{"created":"2023-05-15T14:50:40.842000+00:00","id":69305,"links":{},"metadata":{"_buckets":{"deposit":"33bb6c9d-1718-4d72-a919-9bd7a49c5246"},"_deposit":{"created_by":1,"id":"69305","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"69305"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00069305","sets":["10:28"]},"author_link":["680122","680119","680117","680123","680126","680115","680118","680116","680124","680120","680125","680121"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2008-03-28","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"【目的】生物には，DNA損傷の検出，伝達，修復のために精巧な応答機構が備わっている．中でも，DNA二本鎖切断(DSBs)の修復機構は正常な生体機能を営むために不可欠である．MDC1(Mediator of the DNA-damage Checkpoint 1)は高等真核生物においてDNA損傷応答装置を構成するタンパク質の一つであるが，他の構成タンパク質との相互作用に関しては詳細に理解されていない．今回，ヒト細胞においてMDC1遺伝子欠損細胞を作出し，DNA損傷応答に対するMDC1の役割について検討した．\n【方法】ヒト大腸癌由来HCT116細胞を用いて，標的遺伝子破壊法によりMDC1遺伝子欠損細胞株を作製し，放射線感受性(X線照射後の生存率，染色体異常頻度)を求めた．また，欠損細胞におけるDNA損傷応答タンパク質(g-H2AX, MDC1, 53BP1, ATM)の動態を特異的抗体による免疫細胞化学的染色より検討した．\n【結果・考察】MDC1遺伝子欠損細胞のX線照射後の生存率(D0=0.7Gy,LD10=1.5Gy)は親株(D0=2.4Gy,LD10=3.9Gy)に比べて著しく低下し，染色体異常発現頻度は有意に高くなった．X線照射後のg-H2AX foci形成数は，照射後30分から1時間でピークに達し，その後は徐々に消失傾向にあったが，MDC1遺伝子欠損細胞ではその減衰が緩慢であり，DSBs修復の不全が示された．親株ではg-H2AX fociにMDC1, 53BP1, リン酸化ATM(S1981)が共局在するのに反して，MDC1遺伝子欠損細胞では53BP1, リン酸化ATM(S1981)のg-H2AX fociへの集積は見られなかった．以上のことから，MDC1は53BP1, ATMの局在制御に深く関わり，DSBs周辺のクロマチン微少環境の組織化に重要な役割を果たしている事が明らかになった.","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":"日本薬学会第128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":"小野田, 眞"}],"nameIdentifiers":[{"nameIdentifier":"680115","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森, 雅彦"}],"nameIdentifiers":[{"nameIdentifier":"680116","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"勝部, 孝則"}],"nameIdentifiers":[{"nameIdentifier":"680117","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻, 秀雄"}],"nameIdentifiers":[{"nameIdentifier":"680118","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見, 尚子"}],"nameIdentifiers":[{"nameIdentifier":"680119","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見, 忠博"}],"nameIdentifiers":[{"nameIdentifier":"680120","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小野田 眞","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680121","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森 雅彦","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680122","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"勝部 孝則","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680123","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻 秀雄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680124","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見 尚子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680125","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"塩見 忠博","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680126","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":"MDC1遺伝子欠損ヒト細胞におけるDNA損傷応答の解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"MDC1遺伝子欠損ヒト細胞におけるDNA損傷応答の解析"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2008-03-28"},"publish_date":"2008-03-28","publish_status":"0","recid":"69305","relation_version_is_last":true,"title":["MDC1遺伝子欠損ヒト細胞におけるDNA損傷応答の解析"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:16:03.599687+00:00"}