{"created":"2023-05-15T14:52:25.087166+00:00","id":71568,"links":{},"metadata":{"_buckets":{"deposit":"7c9f6158-90e7-44ec-a916-0f4af3d05f5d"},"_deposit":{"created_by":1,"id":"71568","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71568"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071568","sets":["10:28"]},"author_link":["703852","703849","703857","703856","703858","703848","703844","703847","703850","703851","703855","703846","703845","703854","703853"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2014-11-26","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"DNA二本鎖切断（DSB）は最も細胞障害性の強いDNA損傷であり，高等真核生物では、おもに非相同末端結合（NHEJ）により修復される。XRCC4は，DSBの再結合を担うDNAリガーゼIV複合体の活性および安定性に関与し，NHEJに必須の因子と考えらえている。Artemisは、そのままでは再結合できない複雑なDSBの切断末端を，再結合可能な末端に変換する際に必要なヌクレアーゼで，単純なDSBのNHEJ修復には必須でないと考えらえている。我々は，ヒトのDNA損傷応答におけるXRCC4とArtemisの機能を明らかにするために，ヒト大腸がん由来HCT116細胞株において遺伝子ターゲティング法によりXRCC4欠損細胞(XRCC4-/-)，Artemis欠損細胞(Artemis-/-)を樹立し，各種DNA損傷ストレスに対する細胞応答を検討している。X線照射した細胞の生存率、γH2AXフォーカス、染色体異常の解析から、XRCC4-/-が重篤なDSB修復機能不全を示すのに対し、Artemis-/-のDSB修復機能の低下は限定的であることが示された。主に単純なDSBを生じると考えられるetoposide（DNA topoisomerase II阻害剤）に対して、XRCC4-/-は極めて高い感受性を示したが、Artemis-/-の感受性は親株とほぼ同等であり、単純なDSBの修復にArtemisは必須でないことが示唆された。最近、X線よりも複雑なDSBを生じると考えられる重粒子線に対する感受性の解析に着手した。予備的知見であるが、生存率について親株を基準に比較したところ、XRCC4-/-、Artemis-/-ともに、重粒子線（炭素イオン線、290MeV/u、70KeV/µM）に対する感受性の増加はX線の場合とほぼ同等であった。今後、γH2AXフォーカスの消長や異なる線質の重粒子線に対する感受性を比較検討する予定である。遺伝的背景が均一な遺伝子ターゲティングヒト細胞株を用いることでXRCC4およびArtemisの更なる機能解明が期待される。\n\\nDNA double-strand breaks (DSBs) are the most serious threat to the maintenance of genomic integrity among the different DNA lesions. Non-homologous end-joining (NHEJ) is the predominant repair pathway of DSBs in multicellular eukaryotes. XRCC4, a component of DNA ligase IV complex, is an essential factor for activation and stabilization of the ligase itself in NHEJ. Artemis is believed to function in processing of a subset of complex DNA ends prior to ligation. To better understand the roles of XRCC4 and Artemis in response to DNA damage in humans, we inactivated the XRCC4 and Artemis loci by gene targeting in the human adenocarcinoma somatic cell line HCT116, and assessed cellular responses to various DNA-damaging stress. Analyses of cell survival, γH2AX foci and chromosomal aberrations after X-irradiation demonstrated a serious incompetence of DSB repair in the XRCC4-/- cells, and relatively moderate impairment in Artemis-/- cells. XRCC4-/- showed a prominent increase in sensitivity to etoposide but Artemis-/- did not as compared to HCT116 cells. Artemis may not be required for NHEJ of mostly simple DSBs resulting from inhibition of DNA topoisomerase II by etoposide. Recently, we stated to analyze cellular responses to heavy-ion beams, which are known to introduce DSBs of greater complexity than X-rays. Preliminary analysis of cell survival suggested that increases in sensitivity of both XRCC4-/- and Artemis-/- cells to a carbon-ion beam (290 MeV/u, 70 KeV/µM) were equivalent to those to X-rays. Further analyses of these isogenic mutant cells irradiated with various types of heavy-ion beams will provide insight into the function of Artemis and XRCC4 in humans.","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":"第37回日本分子生物学会年会","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":"勝部, 孝則"}],"nameIdentifiers":[{"nameIdentifier":"703844","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"劉強"}],"nameIdentifiers":[{"nameIdentifier":"703845","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王, 冰"}],"nameIdentifiers":[{"nameIdentifier":"703846","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井, 充"}],"nameIdentifiers":[{"nameIdentifier":"703847","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森, 雅彦"}],"nameIdentifiers":[{"nameIdentifier":"703848","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻, 秀雄"}],"nameIdentifiers":[{"nameIdentifier":"703849","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見, 忠博"}],"nameIdentifiers":[{"nameIdentifier":"703850","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小野田, 眞"}],"nameIdentifiers":[{"nameIdentifier":"703851","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"勝部 孝則","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703852","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703853","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井 充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703854","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森 雅彦","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703855","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻 秀雄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703856","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見 忠博","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703857","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小野田 眞","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703858","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"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":"重粒子線を利用した非相同末端結合修復関連因子XRCC4，Artemisの機能解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"重粒子線を利用した非相同末端結合修復関連因子XRCC4，Artemisの機能解析"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-12-12"},"publish_date":"2014-12-12","publish_status":"0","recid":"71568","relation_version_is_last":true,"title":["重粒子線を利用した非相同末端結合修復関連因子XRCC4，Artemisの機能解析"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:49:48.871751+00:00"}