{"created":"2023-05-15T14:50:29.295577+00:00","id":69045,"links":{},"metadata":{"_buckets":{"deposit":"9c6034a4-c98b-4fea-b01b-28f8bda6a259"},"_deposit":{"created_by":1,"id":"69045","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"69045"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00069045","sets":["10:28"]},"author_link":["677650","677648","677653","677647","677652","677649","677651"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2007-07-12","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Werner syndrome (WS) is a rare human premature aging syndrome caused by mutations in the gene encoding the RecQ helicase WRN. Accumulated evidence indicates that WRN deficiency results in abnormal regulation of telomeres, which possibly correlates with accelerated aging and a high incidence of cancer. Here, we demonstrate that a strain of WS fibroblast cells shows abnormal karyotypes characterized by several complex translocations and 50-fold more frequency of spontaneous abnormal metaphases including dicentric chromosomes without fragments than normal cells when examined at similar culture stages, i.e., almost 30 population doubling numbers (PDN). Further, telomere fluorescence in situ hybridization indicates that the abnormal telomere signals, extra telomere signal and loss of telomere signal, emerge two- to three-fold more frequently in WS cells than in normal cells. Taken together, these results indicate that chromosome instability including dysfunction of telomere maintenance is more prominent in WS cells than in normal cells. In addition, the accumulation of DNA double-strand breaks (DSBs) at the G1 phase, including those co-localized at telomeres, detected by phosphorylated ATM foci is accelerated in WS cells even at a low senescence level, suggesting that lack of WRN contributes to promoting DSB accumulation. The increased accumulation of DSBs in WS cells is substantially reduced in the presence of antioxidant agents, suggesting that enhanced oxidative stress in WS cells is involved in accelerated accumulation of DSBs. Indeed, PDN-dependent increase of intracellular oxidative stress measured by 2070- dichlorodihydrofluorescein diacetate (H2DCFDA) is more accelerated in WS cells than in normal cells. These results indicate that WS cells are prone to accumulate DSBs spontaneously due to a defect of WRN, which leads to increased chromosome instability that could activate checkpoints, resulting in accelerated senescence.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"13th International Congress of Radiation Research","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ariyoshi, Kentaro"}],"nameIdentifiers":[{"nameIdentifier":"677647","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suzuki, Keiji"}],"nameIdentifiers":[{"nameIdentifier":"677648","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kodama, Seiji"}],"nameIdentifiers":[{"nameIdentifier":"677649","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Watanabe, Masami"}],"nameIdentifiers":[{"nameIdentifier":"677650","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"et.al"}],"nameIdentifiers":[{"nameIdentifier":"677651","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有吉 健太郎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"677652","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"児玉 靖司","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"677653","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Increased chromosome instability and accumulation of DNA double-strand breaks in Werner syndrome cells.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Increased chromosome instability and accumulation of DNA double-strand breaks in Werner syndrome cells."}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2007-07-20"},"publish_date":"2007-07-20","publish_status":"0","recid":"69045","relation_version_is_last":true,"title":["Increased chromosome instability and accumulation of DNA double-strand breaks in Werner syndrome cells."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:19:08.355534+00:00"}