{"created":"2023-05-15T14:36:52.101713+00:00","id":47503,"links":{},"metadata":{"_buckets":{"deposit":"b30d25ff-1eff-4364-8398-8624bd5ddc95"},"_deposit":{"created_by":1,"id":"47503","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"47503"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00047503","sets":["1"]},"author_link":["475976","475972","475979","475981","475977","475980","475975","475973","475978","475974"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-01","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"18231-15","bibliographicPageStart":"18231-1","bibliographicVolumeNumber":"5","bibliographic_titles":[{"bibliographic_title":"Scientific reports"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiation, including HP1β-, γH2AX- and Rad51-foci formation. DNMT3B RNAi impaired damage-dependent H2AX accumulation and showed a reduced level of γH2AX induction after γ-irradiation. DNMT3B interacted with HP1β in non-irradiated conditions, whereas irradiation abrogated the DNMT3B/HP1β complex but induced interaction between DNMT3B and H2AX. Consistent with radiosensitization, TP63, BAX, PUMA and NOXA expression was induced after γ-irradiation in DNMT3B knockdown cells. Together with the observation that H2AX overexpression canceled radiosensitization by DNMT3B RNAi, these results suggest that DNMT3B RNAi induced radiosensitization through impairment of damage-dependent HP1β foci formation and efficient γH2AX-induction mechanisms including H2AX accumulation. Enhanced radiosensitivity by DNMT3B RNAi was also observed in a tumor xenograft model. Taken together, the current study implies that comprehensive screening accompanied by a cluster analysis enabled the identification of radiosensitization targets. Downregulation of DNMT3B, one of the targets identified using this method, radiosensitizes cancer cells by disturbing multiple DNA damage responses.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Publishing Group"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"26667181","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/srep18231","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"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":"Fujimori, Hiroaki"}],"nameIdentifiers":[{"nameIdentifier":"475972","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sato, Akira"}],"nameIdentifiers":[{"nameIdentifier":"475973","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kikuhara, Sota"}],"nameIdentifiers":[{"nameIdentifier":"475974","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wang, Junhui"}],"nameIdentifiers":[{"nameIdentifier":"475975","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirai, Takahisa"}],"nameIdentifiers":[{"nameIdentifier":"475976","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Murakami, Yasufumi"}],"nameIdentifiers":[{"nameIdentifier":"475977","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sasaki, Yuka"}],"nameIdentifiers":[{"nameIdentifier":"475978","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okayasu, Ryuichi"}],"nameIdentifiers":[{"nameIdentifier":"475979","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masutani, Mitsuko"}],"nameIdentifiers":[{"nameIdentifier":"475980","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡安 隆一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"475981","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation."}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2016-08-24"},"publish_date":"2016-08-24","publish_status":"0","recid":"47503","relation_version_is_last":true,"title":["A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:39:01.754836+00:00"}