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| 17174478 | WRN | WRN | 3.5 | Fig 6 WRN exonuclease structure and hexameric ring model | |  |
| 17174478 | WRN | WRN | 3.5 | a WRN protein is modular composed of an N-terminal exnuclease domain (blue), | | |
| 17174478 | WRN | WRN | 3.5 | b The WRN exonuclease (more more ... | | |
| 17174478 | WRN | WRN | 3.5 | Double-Strand Breaks Base Excision Repair and WRN | | |
| 17174478 | WRN | WRN | 3.5 | Hereditary mutations in WRN are associated with Werner syndrome (WS), WS a rare autosomal | | |
| 17174478 | WRN | WRN | 3.5 | WRN encodes a 1 432-residue protein that contains a C-terminal nuclear-localization | | |
| 17174478 | WRN | WRN | 3.5 | WRN belongs to the RecQ helicase family that is widely distributed | | |
| 17174478 | WRN | WRN | 3.5 | WRN has been implicated to function in multiple DNA metabolism steps | | |
| 17174478 | WRN | WRN | 3.5 | Biochemical characterization of WRN helicase has shown ATPase activity and unwinding of partial-duplex DNA | | |
| 17174478 | WRN | WRN | 3.5 | Significantly a unique feature of WRN among all the human RecQ helicases is the addition of | | |
| 17174478 | WRN | WRN | 3.5 | WRN exonuclease functions on a variety of structured DNA substrates that | | |
| 17174478 | WRN | WRN | 3.5 | WRN 3_amp_#x02032 -5_amp_#x02032 exonuclease activity shows substrate specificity similar to that | | |
| 17174478 | WRN | WRN | 3.5 | similar to that for the helicase suggesting that the two WRN enzymatic activities may have coordinated functions on several classes of | | |
| 17174478 | WRN | WRN | 3.5 | WRN has been implicated in certain DNA repair events as WS | | |
| 17174478 | WRN | WRN | 3.5 | WRN links to BER include physical and functional interaction with pol_amp_#x003b2 | | |
| 17174478 | WRN | 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. | | |
| 17174478 | WRN | WRN | 3.5 | WRN activity is regulated by holo _amp_#x02013 DNA-PK ( Yannone et | | |
| 17174478 | WRN | WRN | 3.5 | DNA-PK ( Yannone et al. 2001 Karmakar et al. 2002a WRN is an in vivo substrate of DNA-PK ( Yannone et | | |
| 17174478 | WRN | 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 | | |
| 17174478 | WRN | WRN | 3.5 | Furthermore WRN has been observed in an endogenous complex with the Ku70/80 | | |
| 17174478 | WRN | WRN | 3.5 | WRN has a modular composition ( Fig 6a and structural studies | | |
| 17174478 | WRN | WRN | 3.5 | protein's domains and those of homologues are helping to define WRN mediated functions ( Killoran and Keck 2006 | | |
| 17174478 | WRN | WRN | 3.5 | The N-terminus of WRN contains the exonuclease domain the central core contains the helicase | | |
| 17174478 | WRN | WRN | 3.5 | Crystallographic and structure based mutational studies on the WRN exonuclease domain have revealed a high degree of structural and | | |
| 17174478 | WRN | WRN | 3.5 | These structural biochemistry studies on WRN exonuclease revealed a two metal ion mediated mechanism of nucleotide | | |
| 17174478 | WRN | WRN | 3.5 | The lanthanide Eu 3 ions inhibit the WRN exonuclease activity probably due to either a greater charge state | | |
| 17174478 | WRN | WRN | 3.5 | Ku70/80 Ku70 80 specifically stimulates this WRN exonuclease activity but inhibits the Klenow fragment exonuclease its closest | | |
| 17174478 | WRN | 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 | | |
| 17174478 | WRN | WRN | 3.5 | Additionally WRN exonuclease activity is required to fully compliment a Werner syndrome | | |
| 17174478 | WRN | 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 | | |
| 17174478 | WRN | WRN | 3.5 | Melek et al. 1998 Verkaik et al. 2002 possibly linking WRN to this pathway | | |
| 17174478 | WRN | WRN | 3.5 | Werner syndrome cells have mild radiation sensitivity which rules out WRN as an essential DSB repair protein but WRN exonuclease may | | |
| 17174478 | WRN | WRN | 3.5 | rules out WRN as an essential DSB repair protein but WRN exonuclease may nevertheless be used for resolution of a limited | | |
| 17174478 | WRN | WRN | 3.5 | Double-Strand Breaks Base Excision Repair and WRN | | |
| 17174478 | WRN | WRN | 3.5 | This substantial functional divergence between WRN exonuclease and its structural homologs such as Klenow fragment exonuclease | | |
| 17174478 | WRN | WRN | 3.5 | The WRN exonuclease domain construct that was defined by crystallography studies is | | |
| 17174478 | WRN | WRN | 3.5 | However a similar WRN exonuclease construct forms homo-hexamers upon interaction with DNA or PCNA | | |
| 17174478 | WRN | WRN | 3.5 | Also a larger WRN N-terminal construct residues 1-333 and containing the exonuclease domain forms | | |
| 17174478 | WRN | WRN | 3.5 | potentially affects substrate specificities and enzymatic activities of the full-length WRN protein | | |
| 17174478 | WRN | WRN | 3.5 | The multimerization state of WRN homologues is still under debate ( Sharma et al. 2006 | | |
| 17174478 | WRN | WRN | 3.5 | A WRN exonuclease hexameric ring model ( Fig 6c has been built | | |
| 17174478 | WRN | WRN | 3.5 | This WRN exonuclease ring contains a positively charged central cavity with the | | |
| 17174478 | WRN | WRN | 3.5 | Important insights into the molecular mechanisms of WRN have also been discovered from the structure of the conserved | | |
| 17174478 | WRN | WRN | 3.5 | In WRN a mutation in Motif I in mice induces a Werner | | |
| 17174478 | WRN | 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 | | |
| 17174478 | WRN | WRN | 3.5 | a more recently determined NMR structure of this domain in WRN ( Hu et al. 2005 ( Fig 6g | | |
| 17174478 | WRN | WRN | 3.5 | This domain in WRN binds several alternate DNA substructures including forks holding junctions 3_amp_#x02032 | | |
| 17174478 | WRN | WRN | 3.5 | Notably the WRN winged helix domain facilitates targeting of WRN to the nucleolus | | |
| 17174478 | WRN | WRN | 3.5 | Notably the WRN winged helix domain facilitates targeting of WRN to the nucleolus ( von Kobbe and Bohr 2002 and | | |
| 17174478 | WRN | WRN | 3.5 | and interactions of several of the potential protein partners of WRN have also been specifically mapped to this winged helix domain | | |
| 17174478 | WRN | WRN | 3.5 | indicating the critical and versatile nature of this domain in WRN | | |
| 17174478 | WRN | WRN | 3.5 | The remaining C-terminal domain of WRN is the HRDC ( H elicase R Nase D C | | |
| 17174478 | WRN | WRN | 3.5 | In WRN the HRDC domain preferentially binds to forked duplex DNA and | | |
| 17174478 | WRN | WRN | 3.5 | this domain is utilized in replication and recombination functions of WRN | | |
| 17174478 | WRN | WRN | 3.5 | Significantly the interactions with the WRN C-terminus containing the winged helix and HRDC domains have been | | |
| 17174478 | WRN | WRN | 3.5 | HRDC domains have been indicated to regulate the activity of WRN or of the partner protein | | |
| 17174478 | WRN | WRN | 3.5 | The WRN exonuclease domain activity is regulated through the interaction of its | | |
| 17174478 | WRN | WRN | 3.5 | While WRN helicase activity is regulated by C-terminal interactions that include TRF2 | | |
| 17174478 | WRN | WRN | 3.5 | An example of WRN stimulation of partner proteins includes the FEN-1 partner protein whose | | |
| 17174478 | WRN | WRN | 3.5 | WRN interaction that was mapped to the winged helix domain stimulates | | |
| 17174478 | WRN | 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 | | |
| 17174478 | WRN | WRN | 3.5 | or protein interactions may potentially allow for controlled handoffs during WRN mediated pathway progression and how the breakdown of this pathway | | |
| 17174478 | WRN | WRN | 3.5 | breakdown of this pathway progression in the absence of functioning WRN gives rise to the disease phenotype | | |
| 17174478 | WRN | WRN | 3.5 | This includes MRN complex or the WRN RecQ helicase which may prove to be suitable targets for | | |
| 17174478 | 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. | | |
| 17174478 | werner syndrome | werner syndrome | 1.0 | keywords: amyotrophic lateral sclerosis ataxia telangiectasia like disorder werner syndrome xeroderma pigmentosum nitric oxide synthase superoxide dismutase | | |
| 17174478 | 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 . | | |
| 17174478 | 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 | | |
| 17174478 | 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 . | | |
| 17174478 | 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 . | | |
| 17174478 | 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. | | |