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http://purl.uniprot.org/citations/16622405http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16622405http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16622405http://www.w3.org/2000/01/rdf-schema#comment"WRN is unique among the five human RecQ DNA helicases in having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end joining. Metal-ion complex structures, active site mutations and activity assays reveal a nuclease mechanism mediated by two metal ions. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ-family replicative proofreading exonucleases, describing WRN-specific adaptations consistent with double-stranded DNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support DnaQ-like proofreading activities stimulated by Ku70/80, with implications for WRN functions in age-related pathologies and maintenance of genomic integrity."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.org/dc/terms/identifier"doi:10.1038/nsmb1088"xsd:string
http://purl.uniprot.org/citations/16622405http://purl.org/dc/terms/identifier"doi:10.1038/nsmb1088"xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Han S."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Han S."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Tainer J.A."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Tainer J.A."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Cooper P.K."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Cooper P.K."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Holden L.G."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Holden L.G."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Hitomi C."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Hitomi C."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Perry J.J."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Perry J.J."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Chen D.J."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Chen D.J."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Yannone S.M."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Yannone S.M."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Asaithamby A."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/author"Asaithamby A."xsd:string
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16622405http://purl.uniprot.org/core/date"2006"xsd:gYear