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PMID	17174478 ( )
Title	Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
Abstract	This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to various extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.

Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
12791	WRN	Werner syndrome	71	werner syndrome \| WRN \|
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	63	TFIIH \| XPB \| XPB-family \|
7872	NOS1	nitric oxide synthase 1 (neuronal)	37	NOS \| nNOS \| NOS-peptide \| neuronal nitric oxide synthase \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	28	SOD1 \| superoxide dismutase1 \| SOD-mediated \| superoxide dismutase \|
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	21	NER \| NER-specific \|
11180	SOD2	superoxide dismutase 2, mitochondrial	12	manganese superoxide dismutase \| MnSOD \|
1516	CAT	catalase	9	catalase \|
270	PARP1	poly (ADP-ribose) polymerase family, member 1	9	PARP-1 \| poly adp ribose polymerase \| poly adp ribose polymerase 1 \|
9816	RAD50	RAD50 homolog (S. cerevisiae)	8	Rad50 \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	8	iNOS \| nitric oxide synthase \|
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	7	Mre11 \|
3650	FEN1	flap structure-specific endonuclease 1	6	fen 1 \| FEN-1 \|
22948	NLRP2	NLR family, pyrin domain containing 2	6	Nbs1 \|
1058	BLM	Bloom syndrome	6	bloom syndrome \| BLM \|
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	5	eNOS \|
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	5	Ku70 \|
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	5	parp 1 \|
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	5	Rad51 \| RecA-like \|
9413	PRKDC	protein kinase, DNA-activated, catalytic polypeptide	4	DNA-PK \|
12950	SF1	splicing factor 1	4	SF1 \|
8729	PCNA	proliferating cell nuclear antigen	3	PCNA \|
12814	XPA	xeroderma pigmentosum, complementation group A	3	xeroderma pigmentosum \|
9208	POR	P450 (cytochrome) oxidoreductase	2	cytochrome p450 reductase \| nadph dependent cytochrome p450 reductase \|
9824	RAD52	RAD52 homolog (S. cerevisiae)	2	Rad52 \|
795	ATM	ataxia telangiectasia mutated	1	ATM \|
443	ALS2	amyotrophic lateral sclerosis 2 (juvenile)	1	ALS2 \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	1	amyloid-like \|
4739	H2AFX	H2A histone family, member X	1	H2AX \|
9122	PMS2	PMS2 postmeiotic segregation increased 2 (S. cerevisiae)	1	dna mismatch repair \|
445	SETX	senataxin	1	SETX \|
7983	NR5A1	nuclear receptor subfamily 5, group A, member 1	1	sf 1 \|
11729	TERF2	telomeric repeat binding factor 2	1	TRF2 \|
10289	RPA1	replication protein A1, 70kDa	1	RPA \|
9950	RECQL5	RecQ protein-like 5	1	RecQ5 \|
12649	VAPB	VAMP (vesicle-associated membrane protein)-associated protein B and C	1	VAPB \|
11998	TP53	tumor protein p53	1	p53 \|
10780	SFRS1	splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor)	1	SF2 \|
9948	RECQL	RecQ protein-like (DNA helicase Q1-like)	1	RecQ1 \|
1613	CCS	copper chaperone for superoxide dismutase	1	CCS \|
1101	BRCA2	breast cancer 2, early onset	1	BRCA2 \|
11609	TBXAS1	thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A)	1	cytochrome p450 \|
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	1	P450 \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	Fig 1 The Human MnSOD active site
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	In the wild type MnSOD structure (PDB PDB code 1N0J the His26 His74 His163 and
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Fig 2 Proposed holo -NOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	a The modular structure of nNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	This schematic representation shows the domain organization of nNOS indicated above the regions binding the substrate and cofactors below
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Fig 3 Proposed holo -NOS assembly and domain movements
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	a Three possible models for dimeric holo -NOS dimeric NOSox and NOSred modules are represented by pairs of
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	b DNA binding straightens the Rad50 coiled coils which favors inter-complex tethering via Rad50 Zn-hooks with
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	straightens the Rad50 coiled coils which favors inter-complex tethering via Rad50 Zn-hooks with extended and parallel (more more ...
12791	WRN	Werner syndrome	WRN	3.5	Fig 6 WRN exonuclease structure and hexameric ring model
12791	WRN	Werner syndrome	WRN	3.5	a WRN protein is modular composed of an N-terminal exnuclease domain (blue),
12791	WRN	Werner syndrome	WRN	3.5	b The WRN exonuclease (more more ...
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Fig 7 XPB conserved motifs and structural architecture
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	a Schematic alignment between Af XPB Af and human XPB Hs
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	a Schematic alignment between Af XPB Af and human XPB Hs
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Fig 8 Proposed structure-based mechanism whereby damage verification by XPB promotes unwinding of damaged dsDNA for NER
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	damage verification by XPB promotes unwinding of damaged dsDNA for NER
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	a Schematic model shows how XPB DRD depicted in blue HD1 cyan RED motif red HD2
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB Archaeoglobus fulgidus XPB AH auto-inhibitory helix ATLD ataxiatelangiectasia-like disorder BER
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB Archaeoglobus fulgidus XPB AH auto-inhibitory helix ATLD ataxiatelangiectasia-like disorder BER base excision repair
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	helicase RNase D conserved domain MMR mismatch repair MRN Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 mtDNA mitochondrial DNA NER nucleotide excision repair NO
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	RNase D conserved domain MMR mismatch repair MRN Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 mtDNA mitochondrial DNA NER nucleotide excision repair NO nitric
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	D conserved domain MMR mismatch repair MRN Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 mtDNA mitochondrial DNA NER nucleotide excision repair NO nitric oxide
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	mismatch repair MRN Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 mtDNA mitochondrial DNA NER nucleotide excision repair NO nitric oxide e i or nNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	NER nucleotide excision repair NO nitric oxide e i or nNOS endothelial inducible or neuronal nitric oxide synthase NOSox NOS catalytic
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	or nNOS endothelial inducible or neuronal nitric oxide synthase NOSox NOS catalytic oxygenase module NOSred NOS reductase module NHEJ nonhomologous end
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	neuronal nitric oxide synthase NOSox NOS catalytic oxygenase module NOSred NOS reductase module NHEJ nonhomologous end joining ROS reactive oxygen species
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	reductase module NHEJ nonhomologous end joining ROS reactive oxygen species SOD superoxide dismutase SSBs single-strand breaks TC-NER transcription-coupled nucleotide excision repair
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	rapidly scavenged in the cell by the superoxide dismutase (SOD) SOD enzymes
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	SOD enzymes catalyze the disproportionation of superoxide anion radicals to molecular
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	The important role of SOD in the brain was highlighted by genetic inactivation of the
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	was highlighted by genetic inactivation of the mitochondrial form of SOD manganese SOD (MnSOD), MnSOD in mice
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	by genetic inactivation of the mitochondrial form of SOD manganese SOD (MnSOD), MnSOD in mice
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	inactivation of the mitochondrial form of SOD manganese SOD (MnSOD), MnSOD in mice
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	Treatment with an SOD mimetic MnTBAP rescued the MnSOD _amp_#x02212;/_amp_#x02212; _amp_#x02212 _amp_#x02212 mutant mice
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	Treatment with an SOD mimetic MnTBAP rescued the MnSOD _amp_#x02212;/_amp_#x02212; _amp_#x02212 _amp_#x02212 mutant mice from this systemic pathology and
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	of ROS ( Melov et al. 1998 normally removed by MnSOD
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	To define how MnSOD controls ROS levels in the cell the molecular mechanism of
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	controls ROS levels in the cell the molecular mechanism of MnSOD has been extensively characterized through combined structural and biochemical studies
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	The crystal structure of human MnSOD revealed that the enzyme forms a homotetramer ( Borgstahl et
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	suggests that maintenance of the correct hydrogen bond partners in MnSOD is essential for the highly tuned reactivity of the active
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.9	However mutations in the superoxide dismutase1 (SOD1) SOD1 gene give rise to approximately 20% of FALS cases (
443	ALS2	amyotrophic lateral sclerosis 2 (juvenile)	ALS2	1.8	et al. 2002 while mutations in several other genes including ALS2 SETX or VAPB cause much rarer forms of FALS (
445	SETX	senataxin	SETX	0.3	al. 2002 while mutations in several other genes including ALS2 SETX or VAPB cause much rarer forms of FALS ( Kunst
12649	VAPB	VAMP (vesicle-associated membrane protein)-associated protein B and C	VAPB	0.3	while mutations in several other genes including ALS2 SETX or VAPB cause much rarer forms of FALS ( Kunst 2004
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.9	SOD1 encodes a cytosolic copper zinc superoxide dismutase (Cu,Zn Cu Zn
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	encodes a cytosolic copper zinc superoxide dismutase (Cu,Zn Cu Zn SOD which similar to the mitochondrial MnSOD is responsible for the
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	1.9	dismutase (Cu,Zn Cu Zn SOD which similar to the mitochondrial MnSOD is responsible for the disproportionation of harmful superoxide radicals to
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	Structural studies on human Cu Zn SOD have revealed that the enzyme is composed of two identical
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	2.9	A multitude of SOD1 mutations have been identified in FALS patients ( Gaudette et
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	The mutations are dispersed throughout the 153 amino acid residue SOD polypeptide ( Deng et al. 1993
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	data support the idea that toxicity of intracellular Cu Zn SOD aggregates may result from protein misfolding or impaired protein degradation
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	found in the cytoplasm are strongly immunoreactive to Cu Zn SOD antibodies and cannot be dissociated with strong detergents or reducing
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD-mediated	2.9	One proposed mechanism of FALS mutant SOD-mediated toxicity is the coprecipitation of mutant Cu Zn SOD with
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	mutant SOD-mediated toxicity is the coprecipitation of mutant Cu Zn SOD with essential cellular components ( Bruijn et al. 1998 Johnston
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	and this has been demonstrated with the copper chaperone for SOD (CCS)( CCS Kato et al. 2001 nitric oxide synthase (NOS)
1613	CCS	copper chaperone for superoxide dismutase	CCS	1.2	has been demonstrated with the copper chaperone for SOD (CCS)( CCS Kato et al. 2001 nitric oxide synthase (NOS) NOS and
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	(CCS)( CCS Kato et al. 2001 nitric oxide synthase (NOS) NOS and phosphorylated neurofilaments ( Chou et al. 1996
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	is not entirely clear how the many different Cu Zn SOD single-site mutations which are widely dispersed throughout the protein sequence
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	combined structural biochemical and biophysical characterizations of two FALS mutant SOD proteins ( DiDonato et al. 2003
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	3.4	two FALS proteins represent the two major structural classes of SOD mutations
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid-like	1.0	post-mortem studies of FALS patients and bind dyes that detect amyloid-like structure
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	at the synthesis level by the nitric oxide synthase (NOS) NOS enzymes
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The NOS enzymes produce NO through the conversion of arginine to citrulline
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	In mammals there are three NOS isoforms which have been named after the activity or tissue
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	These NOS isoforms are neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	These NOS isoforms are neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS)
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	These NOS isoforms are neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	These NOS isoforms are neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	NOS isoforms are neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS are constitutively
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	neuronal NOS (nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS are constitutively expressed isozymes controlling
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	(nNOS), nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS are constitutively expressed isozymes controlling basal NO
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	nNOS endothelial NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS are constitutively expressed isozymes controlling basal NO levels
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	NOS (eNOS) eNOS and inducible NOS (iNOS) iNOS nNOS and eNOS are constitutively expressed isozymes controlling basal NO levels and synthesizing
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.7	synthesizing NO in response to increases in intracellular calcium levels iNOS is expressed in response to specific cytokines growth factors or
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Functional NOS isozymes are homodimers and each isozyme subunit contains an N-terminal
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	two tetrahydrobiopterin cofactors and a zinc ion that stabilize the NOS dimer interface ( Crane et al. 1998 Raman et al.
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	P450	1.9	NOSred belongs to a large protein family including NADPH-dependent cytochrome P450 reductase and sulfite reductase flavoprotein
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	biochemistry data elucidated from a fully assembled reductase dimer of nNOS ( Fig 2b c provided critical insights into this domain's
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	regulatory element the C-terminal tail and phosphorylation function to regulate NOS activity which is exquisitely tuned to control NO production (
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	In addition eNOS and nNOS contain the 42_amp_#x02013 45-residue auto-inhibitory helix (AH) AH
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	In addition eNOS and nNOS contain the 42_amp_#x02013 45-residue auto-inhibitory helix (AH) AH within the
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	of a protruding _amp_#x003b2 -finger present in the CD of eNOS and nNOS plays an autoinhibitory role in the control of
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	protruding _amp_#x003b2 -finger present in the CD of eNOS and nNOS plays an autoinhibitory role in the control of NO by
7876	NOS3	nitric oxide synthase 3 (endothelial cell)	eNOS	2.2	The upregulation of eNOS and nNOS activity is controlled by phosphorylation of both the
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	The upregulation of eNOS and nNOS activity is controlled by phosphorylation of both the CT and
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	An experimentally determined structure of full-length NOS remains elusive perhaps due to the required flexibility of its
7872	NOS1	nitric oxide synthase 1 (neuronal)	nNOS	2.7	dimer provided a template for a model of the holo -nNOS enzyme assembly ( Garcin et al. 2004
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The NOS model was built by connecting the dimeric NOSox modules and
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS-peptide	2.7	built by connecting the dimeric NOSox modules and a CaM NOS-peptide complex ( Aoyagi et al. 2003 to the NOSred structure
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The flexible hinge region in NOS would serve as the pivot point for this motion (
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	account for the slow rate of inter-module electron transfer in NOS
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The dimerization NOS would provide a means for fine-tuning this electron transfer mechanism
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	Koedel and Pfister 1999 through the calcium-mediated activation of neuronal NOS ( Aoyagi et al. 2003
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	accentuated by NO used in signaling and by stimulation of NOS by calcium burst during invasion
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	Nucleotide excision repair (NER) NER differs from BER by responding to DNA helix distorting damage
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	Evidence for NER in the brain also includes studies on cerebellar extracts (
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	1998 and also a few rare hereditary diseases in known NER genes that cause marked neurological pathology which are discussed later
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	The Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 (MRN) MRN protein complex plays a central role
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	The Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 (MRN) MRN protein complex plays a central role in
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	The Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1 (MRN) MRN protein complex plays a central role in repairing
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	Mutations in the Mre11 component give rise to ataxia-telangiectasia-like disorder (ATLD), ATLD with its
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	Mutations in Nbs1 cause Nijmegen Breakage syndrome which displays similar symptoms to ATLD
795	ATM	ataxia telangiectasia mutated	ATM	0.9	processing events and to cell cycle checkpoint signaling through both ATM checkpoint kinase ( D'Amours and Jackson 2002 van den Bosch
4739	H2AFX	H2A histone family, member X	H2AX	1.6	al. 2003 Assenmacher and Hopfner 2004 and global genome histone H2AX ( Paull et al. 2000
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	head of the complex possesses ATP-stimulated nuclease activity where the Rad50 ATPase controls the Mre11 nuclease
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	possesses ATP-stimulated nuclease activity where the Rad50 ATPase controls the Mre11 nuclease
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	Nbs1 also appears to be part of the head through its
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	to be part of the head through its interactions with Mre11 ( Zhang et al. 2006
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	form an interlocked hook/Zinc/hook hook Zinc hook bridges joining two Rad50 coiled-coils ( Hopfner et al. 2002a
7230	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	Mre11	2.3	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
9816	RAD50	RAD50 homolog (S. cerevisiae)	Rad50	0.6	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
22948	NLRP2	NLR family, pyrin domain containing 2	Nbs1	1.3	Double-Strand Breaks and Mre11/Rad50/Nbs1 Mre11 Rad50 Nbs1
12791	WRN	Werner syndrome	WRN	3.5	Double-Strand Breaks Base Excision Repair and WRN
12791	WRN	Werner syndrome	WRN	3.5	Hereditary mutations in WRN are associated with Werner syndrome (WS), WS a rare autosomal
12791	WRN	Werner syndrome	WRN	3.5	WRN encodes a 1 432-residue protein that contains a C-terminal nuclear-localization
12791	WRN	Werner syndrome	WRN	3.5	WRN belongs to the RecQ helicase family that is widely distributed
9948	RECQL	RecQ protein-like (DNA helicase Q1-like)	RecQ1	1.3	human genome also contains four other RecQ helicase family members RecQ1 BLM RecQ4L and RecQ5
1058	BLM	Bloom syndrome	BLM	1.6	genome also contains four other RecQ helicase family members RecQ1 BLM RecQ4L and RecQ5
9950	RECQL5	RecQ protein-like 5	RecQ5	1.3	four other RecQ helicase family members RecQ1 BLM RecQ4L and RecQ5
1058	BLM	Bloom syndrome	BLM	1.6	Mutations in BLM and RecQ4L cause Bloom syndrome and Rothmund-Thomson syndrome respectively (
12791	WRN	Werner syndrome	WRN	3.5	WRN has been implicated to function in multiple DNA metabolism steps
12791	WRN	Werner syndrome	WRN	3.5	Biochemical characterization of WRN helicase has shown ATPase activity and unwinding of partial-duplex DNA
12791	WRN	Werner syndrome	WRN	3.5	Significantly a unique feature of WRN among all the human RecQ helicases is the addition of
12791	WRN	Werner syndrome	WRN	3.5	WRN exonuclease functions on a variety of structured DNA substrates that
12791	WRN	Werner syndrome	WRN	3.5	WRN 3_amp_#x02032 -5_amp_#x02032 exonuclease activity shows substrate specificity similar to that
12791	WRN	Werner syndrome	WRN	3.5	similar to that for the helicase suggesting that the two WRN enzymatic activities may have coordinated functions on several classes of
12791	WRN	Werner syndrome	WRN	3.5	WRN has been implicated in certain DNA repair events as WS
12791	WRN	Werner syndrome	WRN	3.5	WRN links to BER include physical and functional interaction with pol_amp_#x003b2
10289	RPA1	replication protein A1, 70kDa	RPA	0.6	pol_amp_#x003b4 ( Szekely et al. 2000 replication protein A (RPA)( RPA Brosh et al. 1999 flap endonuclease 1 (FEN-1) FEN-1 (
3650	FEN1	flap structure-specific endonuclease 1	FEN-1	1.9	(RPA)( RPA Brosh et al. 1999 flap endonuclease 1 (FEN-1) FEN-1 ( Brosh et al. 2001b PCNA ( Lebel et al.
8729	PCNA	proliferating cell nuclear antigen	PCNA	0.9	flap endonuclease 1 (FEN-1) FEN-1 ( Brosh et al. 2001b PCNA ( Lebel et al. 1999 and poly(ADP-ribose)polymerase poly ADP-ribose polymerase
270	PARP1	poly (ADP-ribose) polymerase family, member 1	PARP-1	3.4	et al. 1999 and poly(ADP-ribose)polymerase poly ADP-ribose polymerase 1 (PARP-1) PARP-1 ( von Kobbe et al. 2003a
9824	RAD52	RAD52 homolog (S. cerevisiae)	Rad52	0.6	with the MRN complex ( Cheng et al. 2004 and Rad52 ( Baynton et al. 2003 and by colocalization with Rad51
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	Rad51	1.6	Rad52 ( Baynton et al. 2003 and by colocalization with Rad51 in camptothecin-treated cells ( Sakamoto et al. 2001
12791	WRN	Werner syndrome	WRN	3.5	to the NHEJ pathway is indicated by in interactions of WRN with the NHEJ-essential protein kinase DNA-PK ( Yannone et al.
9413	PRKDC	protein kinase, DNA-activated, catalytic polypeptide	DNA-PK	1.2	by in interactions of WRN with the NHEJ-essential protein kinase DNA-PK ( Yannone et al. 2001 Karmakar et al. 2002a Li
12791	WRN	Werner syndrome	WRN	3.5	WRN activity is regulated by holo _amp_#x02013 DNA-PK ( Yannone et
9413	PRKDC	protein kinase, DNA-activated, catalytic polypeptide	DNA-PK	1.2	WRN activity is regulated by holo _amp_#x02013 DNA-PK ( Yannone et al. 2001 Karmakar et al. 2002a WRN
12791	WRN	Werner syndrome	WRN	3.5	DNA-PK ( Yannone et al. 2001 Karmakar et al. 2002a WRN is an in vivo substrate of DNA-PK ( Yannone et
9413	PRKDC	protein kinase, DNA-activated, catalytic polypeptide	DNA-PK	1.2	et al. 2002a WRN is an in vivo substrate of DNA-PK ( Yannone et al. 2001 Karmakar et al. 2002a and
9413	PRKDC	protein kinase, DNA-activated, catalytic polypeptide	DNA-PK	1.2	Yannone et al. 2001 Karmakar et al. 2002a and the DNA-PK subunit Ku70/80 Ku70 80 stimulates WRN exonuclease activity in vitro
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	Ku70	1.6	2001 Karmakar et al. 2002a and the DNA-PK subunit Ku70/80 Ku70 80 stimulates WRN exonuclease activity in vitro ( Cooper et
12791	WRN	Werner syndrome	WRN	3.5	al. 2002a and the DNA-PK subunit Ku70/80 Ku70 80 stimulates WRN exonuclease activity in vitro ( Cooper et al. 2000 Li
12791	WRN	Werner syndrome	WRN	3.5	Furthermore WRN has been observed in an endogenous complex with the Ku70/80
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	Ku70	1.6	has been observed in an endogenous complex with the Ku70/80 Ku70 80 subunit and poly(ADP-ribose) poly ADP-ribose polymerase-1 (PARP-1) PARP-1 (
270	PARP1	poly (ADP-ribose) polymerase family, member 1	PARP-1	3.4	Ku70/80 Ku70 80 subunit and poly(ADP-ribose) poly ADP-ribose polymerase-1 (PARP-1) PARP-1 ( Li et al. 2004
270	PARP1	poly (ADP-ribose) polymerase family, member 1	PARP-1	3.4	Notably PARP-1 binds sites of SSBs and DSBs and is also implicated
12791	WRN	Werner syndrome	WRN	3.5	WRN has a modular composition ( Fig 6a and structural studies
12791	WRN	Werner syndrome	WRN	3.5	protein's domains and those of homologues are helping to define WRN mediated functions ( Killoran and Keck 2006
12791	WRN	Werner syndrome	WRN	3.5	The N-terminus of WRN contains the exonuclease domain the central core contains the helicase
12791	WRN	Werner syndrome	WRN	3.5	Crystallographic and structure based mutational studies on the WRN exonuclease domain have revealed a high degree of structural and
12791	WRN	Werner syndrome	WRN	3.5	These structural biochemistry studies on WRN exonuclease revealed a two metal ion mediated mechanism of nucleotide
12791	WRN	Werner syndrome	WRN	3.5	The lanthanide Eu 3 ions inhibit the WRN exonuclease activity probably due to either a greater charge state
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	Ku70	1.6	Ku70/80 Ku70 80 specifically stimulates this WRN exonuclease activity but inhibits the
12791	WRN	Werner syndrome	WRN	3.5	Ku70/80 Ku70 80 specifically stimulates this WRN exonuclease activity but inhibits the Klenow fragment exonuclease its closest
12791	WRN	Werner syndrome	WRN	3.5	This also suggests that the WRN exonuclease domain may help impart functions mediated by WRN_amp_#x02013;Ku70/80 WRN_amp_#x02013
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	Ku70	1.6	exonuclease domain may help impart functions mediated by WRN_amp_#x02013;Ku70/80 WRN_amp_#x02013 Ku70 80
12791	WRN	Werner syndrome	WRN	3.5	Additionally WRN exonuclease activity is required to fully compliment a Werner syndrome
12791	WRN	Werner syndrome	WRN	3.5	specific cellular pathway but the elevated microhomology-mediated repair observed in WRN exonuclease deficient cells is similar to the phenotypes associated with
12791	WRN	Werner syndrome	WRN	3.5	Melek et al. 1998 Verkaik et al. 2002 possibly linking WRN to this pathway
12791	WRN	Werner syndrome	WRN	3.5	Werner syndrome cells have mild radiation sensitivity which rules out WRN as an essential DSB repair protein but WRN exonuclease may
12791	WRN	Werner syndrome	WRN	3.5	rules out WRN as an essential DSB repair protein but WRN exonuclease may nevertheless be used for resolution of a limited
12791	WRN	Werner syndrome	WRN	3.5	Double-Strand Breaks Base Excision Repair and WRN
12791	WRN	Werner syndrome	WRN	3.5	This substantial functional divergence between WRN exonuclease and its structural homologs such as Klenow fragment exonuclease
12791	WRN	Werner syndrome	WRN	3.5	The WRN exonuclease domain construct that was defined by crystallography studies is
12791	WRN	Werner syndrome	WRN	3.5	However a similar WRN exonuclease construct forms homo-hexamers upon interaction with DNA or PCNA
8729	PCNA	proliferating cell nuclear antigen	PCNA	0.9	WRN exonuclease construct forms homo-hexamers upon interaction with DNA or PCNA ( Xue et al. 2002
12791	WRN	Werner syndrome	WRN	3.5	Also a larger WRN N-terminal construct residues 1-333 and containing the exonuclease domain forms
12791	WRN	Werner syndrome	WRN	3.5	potentially affects substrate specificities and enzymatic activities of the full-length WRN protein
12791	WRN	Werner syndrome	WRN	3.5	The multimerization state of WRN homologues is still under debate ( Sharma et al. 2006
1058	BLM	Bloom syndrome	BLM	1.6	debate ( Sharma et al. 2006 but the human homolog BLM has been observed to form hexameric and/or and or tetrameric
12791	WRN	Werner syndrome	WRN	3.5	A WRN exonuclease hexameric ring model ( Fig 6c has been built
12791	WRN	Werner syndrome	WRN	3.5	This WRN exonuclease ring contains a positively charged central cavity with the
12791	WRN	Werner syndrome	WRN	3.5	Important insights into the molecular mechanisms of WRN have also been discovered from the structure of the conserved
12950	SF1	splicing factor 1	SF1	0.3	al. 2003 ( Fig 6e and this is similar to SF1 _amp_#x00026 2 helicases
12791	WRN	Werner syndrome	WRN	3.5	In WRN a mutation in Motif I in mice induces a Werner
12950	SF1	splicing factor 1	SF1	0.3	still undefined but the lobes likely use strategies similar to SF1 _amp_#x00026 2 proteins
12950	SF1	splicing factor 1	SF1	0.3	Wang et al. 2000 and regions of sequence similarity to SF1 indicates that WRN helicase may function a base-flipping mechanism proposed
12791	WRN	Werner syndrome	WRN	3.5	2000 and regions of sequence similarity to SF1 indicates that WRN helicase may function a base-flipping mechanism proposed in SF1 despite
12950	SF1	splicing factor 1	SF1	0.3	that WRN helicase may function a base-flipping mechanism proposed in SF1 despite overall sequence similarity to SF2 helicases ( Bernstein et
10780	SFRS1	splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor)	SF2	0.3	base-flipping mechanism proposed in SF1 despite overall sequence similarity to SF2 helicases ( Bernstein et al. 2003
1058	BLM	Bloom syndrome	BLM	1.6	and are sufficient to cause Bloom syndrome when mutated in BLM ( Ellis et al. 1995
12791	WRN	Werner syndrome	WRN	3.5	a more recently determined NMR structure of this domain in WRN ( Hu et al. 2005 ( Fig 6g
12791	WRN	Werner syndrome	WRN	3.5	This domain in WRN binds several alternate DNA substructures including forks holding junctions 3_amp_#x02032
12791	WRN	Werner syndrome	WRN	3.5	Notably the WRN winged helix domain facilitates targeting of WRN to the nucleolus
12791	WRN	Werner syndrome	WRN	3.5	Notably the WRN winged helix domain facilitates targeting of WRN to the nucleolus ( von Kobbe and Bohr 2002 and
12791	WRN	Werner syndrome	WRN	3.5	and interactions of several of the potential protein partners of WRN have also been specifically mapped to this winged helix domain
12791	WRN	Werner syndrome	WRN	3.5	indicating the critical and versatile nature of this domain in WRN
12791	WRN	Werner syndrome	WRN	3.5	The remaining C-terminal domain of WRN is the HRDC ( H elicase R Nase D C
12791	WRN	Werner syndrome	WRN	3.5	In WRN the HRDC domain preferentially binds to forked duplex DNA and
12791	WRN	Werner syndrome	WRN	3.5	this domain is utilized in replication and recombination functions of WRN
12791	WRN	Werner syndrome	WRN	3.5	Significantly the interactions with the WRN C-terminus containing the winged helix and HRDC domains have been
12791	WRN	Werner syndrome	WRN	3.5	HRDC domains have been indicated to regulate the activity of WRN or of the partner protein
12791	WRN	Werner syndrome	WRN	3.5	The WRN exonuclease domain activity is regulated through the interaction of its
11998	TP53	tumor protein p53	p53	0.6	activity is regulated through the interaction of its C-terminus with p53 ( Blander et al. 1999 Ku70/80 Ku70 80 ( Cooper
4055	XRCC6	X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)	Ku70	1.6	its C-terminus with p53 ( Blander et al. 1999 Ku70/80 Ku70 80 ( Cooper et al. 2000 Li and Comai 2000
270	PARP1	poly (ADP-ribose) polymerase family, member 1	PARP-1	3.4	2000 Brosh et al. 2001a Karmakar et al. 2002b and PARP-1 ( von Kobbe et al. 2004
12791	WRN	Werner syndrome	WRN	3.5	While WRN helicase activity is regulated by C-terminal interactions that include TRF2
11729	TERF2	telomeric repeat binding factor 2	TRF2	1.6	WRN helicase activity is regulated by C-terminal interactions that include TRF2 ( Opresko et al. 2002 Rad52 ( Baynton et al.
9824	RAD52	RAD52 homolog (S. cerevisiae)	Rad52	0.6	C-terminal interactions that include TRF2 ( Opresko et al. 2002 Rad52 ( Baynton et al. 2003 and PARP-1 ( von Kobbe
270	PARP1	poly (ADP-ribose) polymerase family, member 1	PARP-1	3.4	et al. 2002 Rad52 ( Baynton et al. 2003 and PARP-1 ( von Kobbe et al. 2004
12791	WRN	Werner syndrome	WRN	3.5	An example of WRN stimulation of partner proteins includes the FEN-1 partner protein whose
3650	FEN1	flap structure-specific endonuclease 1	FEN-1	1.9	An example of WRN stimulation of partner proteins includes the FEN-1 partner protein whose structures with DNA and PCNA have been
8729	PCNA	proliferating cell nuclear antigen	PCNA	0.9	includes the FEN-1 partner protein whose structures with DNA and PCNA have been defined ( Hosfield et al. 1998 Chapados et
12791	WRN	Werner syndrome	WRN	3.5	WRN interaction that was mapped to the winged helix domain stimulates
3650	FEN1	flap structure-specific endonuclease 1	FEN-1	1.9	interaction that was mapped to the winged helix domain stimulates FEN-1 nucleolytic activity by more than 80-fold ( Brosh et al.
12791	WRN	Werner syndrome	WRN	3.5	interesting to define how these interactions are able to regulate WRN catalytic activities how key DNA and/or and or protein interactions
12791	WRN	Werner syndrome	WRN	3.5	or protein interactions may potentially allow for controlled handoffs during WRN mediated pathway progression and how the breakdown of this pathway
12791	WRN	Werner syndrome	WRN	3.5	breakdown of this pathway progression in the absence of functioning WRN gives rise to the disease phenotype
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	NER and the XPB helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	NER and the XPB helicase
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	NER functions to restore short segments of nucleotides containing DNA helix
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	generated by ionizing radiation can produce DNA lesions that require NER for repair ( Satoh et al. 1993
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	NER is a particularly versatile DNA repair system that is capable
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	Hereditary mutations in NER genes clearly demonstrate that the inherited DNA repair potential has
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	Moreover much of our understanding of NER has been derived from studies on cells from individuals with
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	has been derived from studies on cells from individuals with NER defects that present clinical phenotypes
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	gene that is associated with all three disorders is the XPB helicase ( Weeda et al. 1997 which is part of
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	al. 1997 which is part of the general transcription factor TFIIH complex ( Schaeffer et al. 1993
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	The XPB ATPase and helicase activities are essential for promoter DNA melting
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	In addition to these transcriptional functions XPB also plays a role in NER
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	to these transcriptional functions XPB also plays a role in NER
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Recent developments in structural and biochemical characterization of XPB helicase have begun to address some of the key questions
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	of the key questions on the underlying mechanisms of how XPB and TFIIH function in both transcription and NER ( Coin
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	key questions on the underlying mechanisms of how XPB and TFIIH function in both transcription and NER ( Coin et al.
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	of how XPB and TFIIH function in both transcription and NER ( Coin et al. 2004 Coin et al. 2006 Fan
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	studies have been conducted on a homolog of the human XPB the archea Archaeoglobus fulgidus XPB ( Af XPB ( Fan
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	a homolog of the human XPB the archea Archaeoglobus fulgidus XPB ( Af XPB ( Fan et al. 2006a
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	the human XPB the archea Archaeoglobus fulgidus XPB ( Af XPB ( Fan et al. 2006a
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB shares 42% amino acid sequence similarity with the central region
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	amino acid sequence similarity with the central region of human XPB suggesting that the core XPB structure is conserved
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	the central region of human XPB suggesting that the core XPB structure is conserved
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	As indicated by sequence comparison the Af XPB structure contains two RecA-like helicase domains (HD1 HD1 and HD2
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	RecA-like	1.6	indicated by sequence comparison the Af XPB structure contains two RecA-like helicase domains (HD1 HD1 and HD2 that belong to helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	However several other functional regions in XPB were discovered that were not predicted either through sequence analysis
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	This domain in Af XPB has been demonstrated to interact with some types of damaged
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	XPB DRD differs from the MutS domain by lacking a critical
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Instead Af XPB DRD likely recognizes distortions in the DNA typically caused by
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	in the DNA typically caused by the broad spectrum of NER lesions
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	is located and linked to initiation of DNA unwinding during NER steps by XPB/TFIIH XPB TFIIH
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	to initiation of DNA unwinding during NER steps by XPB/TFIIH XPB TFIIH
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	initiation of DNA unwinding during NER steps by XPB/TFIIH XPB TFIIH
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB-family	2.4	Also present is a highly conserved XPB-family specific RED amino acid motif located in domain HD1 (
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Mutational analysis suggests that this XPB RED motif has a critical role in DNA unwinding function
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	NER and the XPB helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	NER and the XPB helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB seems to follow this general trend
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	helicase domains HD1 and HD2 observed in the full-length Af XPB is different than the _amp_#x0201c closed_amp_#x0201d conformation observed in crystal
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	also lead to a proposed mechanism for the involvement of XPB in the unwinding of duplex DNA at sites of DNA
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	When XPB is recruited to DNA the DRD domain is proposed to
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	helicase domain HD2 via a rotation of ~170_amp_#x000b0 and allows XPB to wrap around the DNA
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	such a conformational change may result from interaction of the XPB C-terminus (including including ThM and HD2 domains with 3'-overhanging DNA
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	_amp_#x0201c wedge_amp_#x0201d to unzip the DNA when ATP hydrolysis drives XPB to move along the duplex DNA during NER
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	hydrolysis drives XPB to move along the duplex DNA during NER
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	However it is noticed that DNA melting by XPB during transcription initiation is possibly mediated through an unconventional helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	unconventional helicase mechanism ( Kim et al. 2000 in which XPB functions as a molecular _amp_#x0201c wrench_amp_#x0201d rotating downstream DNA relative
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Therefore the conformation observed in the Af XPB structure may represent a _amp_#x0201c transcriptional mode_amp_#x0201d of XPB tuned
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB structure may represent a _amp_#x0201c transcriptional mode_amp_#x0201d of XPB tuned for this action whereas the domain reorientation described above
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER-specific	0.3	for this action whereas the domain reorientation described above is NER-specific and only occurs upon the interactions of the DRD with
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	If these mechanisms are true the conformation of XPB will decide whether TFIIH functions as a transcription factor or
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	mechanisms are true the conformation of XPB will decide whether TFIIH functions as a transcription factor or a DNA repair factor
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	In other words XPB acts as a master key helping TFIIH switch pathway selection
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	In other words XPB acts as a master key helping TFIIH switch pathway selection for transcription or DNA repair whenever it
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	NER and the XPB helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	NER and the XPB helicase
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Defining the Af XPB structural biochemistry has uncovered some unexpected structural motifs and functions
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	biochemistry has uncovered some unexpected structural motifs and functions for XPB
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	However Af XPB only correlates to the central region of human XPB
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB only correlates to the central region of human XPB
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	exclusively occur in the N- and C-terminal extensions of human XPB suggesting that mutation to the conserved XPB central region is
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	extensions of human XPB suggesting that mutation to the conserved XPB central region is lethal
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB reflects the basic structure and function of XPB helicases
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Af XPB reflects the basic structure and function of XPB helicases
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	However the extensions to the human XPB are likely to contribute to a greater level of complexity
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	Phosphorylation of residue S751 at the C-terminal extension of human XPB was reported to regulate TFIIH activity in NER reactions (
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	the C-terminal extension of human XPB was reported to regulate TFIIH activity in NER reactions ( Coin et al. 2004
7965	NR1H2	nuclear receptor subfamily 1, group H, member 2	NER	1.3	of human XPB was reported to regulate TFIIH activity in NER reactions ( Coin et al. 2004
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	The physical and functional interactions between XPB and other proteins within and outside of the TFIIH complex
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	between XPB and other proteins within and outside of the TFIIH complex have been investigated recently ( Jawhari et al. 2002
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	occur in the extensions and have profound effects on the TFIIH activities in transcription or DNA repair
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	XPB	2.4	that future studies will similarly uncover new functions for human XPB
3435	ERCC3	excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	TFIIH	2.7	features highlighted above will fit into the ring-structure of human TFIIH complex ( Chang and Kornberg 2000 Schultz et al. 2000
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	significant example is the fine control of activities of the NOS holo-enzyme suggested to occur through either promoting or inhibiting a
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	Rad51	1.6	A significant example of protein interface mimicry occurs in Rad51 filament formation which is central to HRR steps
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	Rad51	1.6	that filament formation occurs by the sequential binding of adjacent Rad51 monomers mimicking a BRC repeat
1101	BRCA2	breast cancer 2, early onset	BRCA2	0.8	This BRC repeat is normally found in the BRCA2 partner that mediates critical functions of Rad51 ( Pellegrini et
9817	RAD51	RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)	Rad51	1.6	found in the BRCA2 partner that mediates critical functions of Rad51 ( Pellegrini et al. 2002 Shin et al. 2003
12791	WRN	Werner syndrome	WRN	3.5	This includes MRN complex or the WRN RecQ helicase which may prove to be suitable targets for
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	2.7	The NOS isoforms also have multiple functions that may be targets for
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	mutations in a superoxide dismutase which removes oxygen free radicals may cause the neurodegenerative disease amyotrophic lateral sclerosis.
12791	WRN	Werner syndrome	werner syndrome	1.0	additionally dna repair disorders that affect the brain to varying extents include ataxia telangiectasia like disorder cockayne syndrome or werner syndrome.
12791	WRN	Werner syndrome	werner syndrome	1.0	keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase
12814	XPA	xeroderma pigmentosum, complementation group A	xeroderma pigmentosum	1.0	keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase
12791	WRN	Werner syndrome	werner syndrome	1.0	severe neurodegeneration is clearly apparent in some disorders such as cockayne syndrome lehmann 2003 while more aging related phenotypes are present in others including werner syndrome goto 1997 .
7872	NOS1	nitric oxide synthase 1 (neuronal)	neuronal nitric oxide synthase	1.0	tion repair hrdc helicase rnase d conserved domain mmr mismatch repair mrn mre11/rad50/nbs1 mtdna mitochondrial dna ner nucleotide excision repair no nitric oxide e i or nnos endothelial inducible or neuronal nitric oxide synthase nosox nos catalytic oxygenase module nosred nos reductase module nhej nonhomologous end joining ros reactive oxygen species sod superoxide dismutase ssbs single strand breaks tc ner transcription cou
12791	WRN	Werner syndrome	werner syndrome	1.0	omologous end joining ros reactive oxygen species sod superoxide dismutase ssbs single strand breaks tc ner transcription coupled nucleotide excision repair thm thumb domain ttd trichothiodystropy ws werner syndrome xp xeroderma pigmentosum
12814	XPA	xeroderma pigmentosum, complementation group A	xeroderma pigmentosum	1.0	ng ros reactive oxygen species sod superoxide dismutase ssbs single strand breaks tc ner transcription coupled nucleotide excision repair thm thumb domain ttd trichothiodystropy ws werner syndrome xp xeroderma pigmentosum
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	ide e i or nnos endothelial inducible or neuronal nitric oxide synthase nosox nos catalytic oxygenase module nosred nos reductase module nhej nonhomologous end joining ros reactive oxygen species sod superoxide dismutase ssbs single strand breaks tc ner transcription coupled nucleotide excision repair thm thumb domain ttd trichothiodystropy ws werner syndrome xp xeroderma pigmentosum
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	ros removal by manganese superoxide dismutase
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	most of these free radicals are rapidly scavenged in the cell by the superoxide dismutase sod enzymes.
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	ros removal by manganese superoxide dismutase
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	ros and copper zinc superoxide dismutase
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase1	1.0	however mutations in the superoxide dismutase1 sod1 gene give rise to approximately 20% of fals cases deng et al. 1993 rosen et al. 1993 rakhit et al. 2002 while mutations in several other genes including als2 setx or vapb cause much rarer forms
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	sod1 encodes a cytosolic copper zinc superoxide dismutase cu zn sod which similar to the mitochondrial mnsod is responsible for the disproportionation of harmful superoxide radicals to hydrogen peroxide and oxygen fridovich 1986 .
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	cu zn sod with essential cellular components bruijn et al. 1998 johnston et al. 2000 cleveland and rothstein 2001 and this has been demonstrated with the copper chaperone for sod ccs kato et al. 2001 nitric oxide synthase nos and phosphorylated neurofilaments chou et al. 1996 .
1516	CAT	catalase	catalase	1.0	the catalase protein completes the process of eliminating ros by converting hydrogen peroxide into water and oxygen.
1516	CAT	catalase	catalase	1.0	in addition to this defense against oxidative damage human catalase has roles in ethanol metabolism zimatkin et al. 1998 inflammation halliwell and gutteridge 1984 apoptosis yabuki et al. 1999 aging and cancer miyamoto et al. 1996 .
1516	CAT	catalase	catalase	1.0	several catalase crystal structures have been determined aiding our understanding of reactive oxygen control by defining the reaction and inhibition mechanisms goth 1997 .
1516	CAT	catalase	catalase	1.0	these studies include the definition of the chemistry of the human catalase through structures of the resting state enzyme and complexes of a catalase bound to cyanide and 3at inhibitors putnam et al. 2000 .
1516	CAT	catalase	catalase	1.0	human catalase forms a tetrameric assembly and this may be important to ensure that the active site is sequestered and that the enzyme is competent to complete the reaction.
1516	CAT	catalase	catalase	1.0	interestingly an unstable catalase isolated from patients homozygous for a swiss type acatalasemia a hereditary catalase deficiency disorder rapidly disassociates into inactive dimers with reduced heme content.
1516	CAT	catalase	catalase	1.0	this suggests that catalase assembly variants may play roles in disease susceptibility aebi et al. 1974 in addition to nonsense and splicing mutations hirono et al. 1995 .
1516	CAT	catalase	catalase	1.0	from the structural data a mechanism for the recognition and removal of peroxide by catalase has been proposed putnam et al. 2000 .
1516	CAT	catalase	catalase	1.0	catalase uses these two asymmetric interactions with the substrate to prime the otherwise symmetric peroxide bond for heterolytic bond cleavage; good geometry for both iron coordination and hydrogen bond form
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	ros and nitric oxide synthase
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	no is a small easily diffusible and transient free radical whose availability is controlled at the synthesis level by the nitric oxide synthase nos enzymes.
9208	POR	P450 (cytochrome) oxidoreductase	nadph dependent cytochrome p450 reductase	1.0	nosred belongs to a large protein family including nadph dependent cytochrome p450 reductase and sulfite reductase flavoprotein.
9208	POR	P450 (cytochrome) oxidoreductase	cytochrome p450 reductase	1.0	nosred belongs to a large protein family including nadph dependent cytochrome p450 reductase and sulfite reductase flavoprotein.
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	ros and nitric oxide synthase
11609	TBXAS1	thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A)	cytochrome p450	1.0	this model is consistent with the proposed role of the same region in the structurally related cytochrome p450 bm3 sevrioukova et al. 1999 and reminiscent of those found in multiple redox centers containing proteins zhang et al. 1998 lennon et al. 2000 leys et al. 2003 .
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	ros and nitric oxide synthase
12791	WRN	Werner syndrome	werner syndrome	1.0	hereditary mutations in wrn are associated with werner syndrome ws a rare autosomal recessive disorder that gives rise to multiple progeroid pathologies including osteoporosis atherosclerosis and a greatly increased cancer incidence goto 1997 .
1058	BLM	Bloom syndrome	bloom syndrome	1.0	mutations in blm and recq4l cause bloom syndrome and rothmund thomson syndrome respectively harrigan et al. 2003 .
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	parp 1	1.0	rigan et al. 2003 pol_amp_#x003b4; szekely et al. 2000 replication protein a rpa brosh et al. 1999 flap endonuclease 1 fen 1 brosh et al. 2001b pcna lebel et al. 1999 and poly adp ribose polymerase 1 parp 1 von kobbe et al. 2003a .
3650	FEN1	flap structure-specific endonuclease 1	fen 1	1.0	inks to ber include physical and functional interaction with pol_amp_#x003b2; harrigan et al. 2003 pol_amp_#x003b4; szekely et al. 2000 replication protein a rpa brosh et al. 1999 flap endonuclease 1 fen 1 brosh et al. 2001b pcna lebel et al. 1999 and poly adp ribose polymerase 1 parp 1 von kobbe et al. 2003a .
270	PARP1	poly (ADP-ribose) polymerase family, member 1	poly adp ribose polymerase	1.0	ion with pol_amp_#x003b2; harrigan et al. 2003 pol_amp_#x003b4; szekely et al. 2000 replication protein a rpa brosh et al. 1999 flap endonuclease 1 fen 1 brosh et al. 2001b pcna lebel et al. 1999 and poly adp ribose polymerase 1 parp 1 von kobbe et al. 2003a .
270	PARP1	poly (ADP-ribose) polymerase family, member 1	poly adp ribose polymerase 1	1.0	ion with pol_amp_#x003b2; harrigan et al. 2003 pol_amp_#x003b4; szekely et al. 2000 replication protein a rpa brosh et al. 1999 flap endonuclease 1 fen 1 brosh et al. 2001b pcna lebel et al. 1999 and poly adp ribose polymerase 1 parp 1 von kobbe et al. 2003a .
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	parp 1	1.0	furthermore wrn has been observed in an endogenous complex with the ku70/80 subunit and poly adp ribose polymerase 1 parp 1 li et al. 2004 .
270	PARP1	poly (ADP-ribose) polymerase family, member 1	poly adp ribose polymerase	1.0	furthermore wrn has been observed in an endogenous complex with the ku70/80 subunit and poly adp ribose polymerase 1 parp 1 li et al. 2004 .
270	PARP1	poly (ADP-ribose) polymerase family, member 1	poly adp ribose polymerase 1	1.0	furthermore wrn has been observed in an endogenous complex with the ku70/80 subunit and poly adp ribose polymerase 1 parp 1 li et al. 2004 .
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	parp 1	1.0	notably parp 1 binds sites of ssbs and dsbs and is also implicated in the control of genomic integrity and mammalian life span burkle et al. 2005 .
12791	WRN	Werner syndrome	werner syndrome	1.0	additionally wrn exonuclease activity is required to fully compliment a werner syndrome dna end joining phenotype in an in vivo plasmid based assay perry et al. 2006 .
12791	WRN	Werner syndrome	werner syndrome	1.0	however werner syndrome cells have mild radiation sensitivity which rules out wrn as an essential dsb repair protein but wrn exonuclease may nevertheless be used for resolution of a limited class of dsbs.
7983	NR5A1	nuclear receptor subfamily 5, group A, member 1	sf 1	1.0	the two n terminal domains are helicase lobes that share structural similar to superfamily sf 1 and 2 helicases but have some features unique to the recq family.
1058	BLM	Bloom syndrome	bloom syndrome	1.0	the cysteine side chains are conserved in the recq family and mutations in these residues disrupt recq helicase function and are sufficient to cause bloom syndrome when mutated in blm ellis et al. 1995 .
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	parp 1	1.0	onuclease domain activity is regulated through the interaction of its c terminus with p53 blander et al. 1999 ku70/80 cooper et al. 2000 li and comai 2000 brosh et al. 2001a karmakar et al. 2002b and parp 1 von kobbe et al. 2004 .
23696	TIPARP	TCDD-inducible poly(ADP-ribose) polymerase	parp 1	1.0	while wrn helicase activity is regulated by c terminal interactions that include trf2 opresko et al. 2002 rad52 baynton et al. 2003 and parp 1 von kobbe et al. 2004 .
3650	FEN1	flap structure-specific endonuclease 1	fen 1	1.0	an example of wrn stimulation of partner proteins includes the fen 1 partner protein whose structures with dna and pcna have been defined hosfield et al. 1998 chapados et al. 2004 .
3650	FEN1	flap structure-specific endonuclease 1	fen 1	1.0	wrn interaction that was mapped to the winged helix domain stimulates fen 1 nucleolytic activity by more than 80 fold brosh et al. 2001b .
12814	XPA	xeroderma pigmentosum, complementation group A	xeroderma pigmentosum	1.0	this includes patients with the rare genetic disorders xeroderma pigmentosum xp trichothiodystrophy ttd and cockayne syndrome cs .
9122	PMS2	PMS2 postmeiotic segregation increased 2 (S. cerevisiae)	dna mismatch repair	1.0	a small n terminal domain is attached to helicase domain hd1 fig 7 which shares structural similarity to the mismatch recognition domain of the dna mismatch repair protein muts obmolova et al. 2000 .