{"created":"2023-07-27T06:51:00.034563+00:00","id":44225,"links":{},"metadata":{"_buckets":{"deposit":"1f1c08cd-dc7b-463b-878d-25e5dbd03239"},"_deposit":{"created_by":18,"id":"44225","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44225"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044225","sets":["2812:2813:2826"]},"author_link":["74376","74377"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-05","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"9p.","bibliographicVolumeNumber":"2006-2007","bibliographic_titles":[{"bibliographic_title":"平成19(2007)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2007 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"DNA二重鎖切断等のDNA損傷応答に中心的な役割を果たしているATMの下流で,c-AblチロシンキナーゼがATM依存性に,DNA相同組み換えタンパク質RAD51をリン酸化するが,相同組み換え修復経路におけるRAD51の多岐にわたる機能のうちのどの部分に関わるかは明らかではない.我々は,c-Ablのクロマチン結合はGlivecで阻害され,Kinase-dead変異体では起こらないことを明らかにした.また最近新たに同定したRAD51-R167G変異体(R167G)は,単独発現ではクロマチンに集積しないが,c-Ablとの共発現により,RAD51野生型と同様に,クロマチン分画に集積し,抗Y-54pあるいはY-315p特異抗体を用いた解析により,c-AblによるRad51の54番,315番のチロシンのリン酸化がクロマチン分画でのみ起こることを認めた.R167Gは,RAD51がフィラメントを形成した時に,隣接するRAD51分子との境界領域に存在すると考えられている.やはり,この領域に存在すると予想されるRAD51-F86E変異体(ケンブリッジ大,Venkitaraman博士から供与された.)についても,c-Ablとの共発現でクロマチン集積が回復し,54番,315番のチロシンリン酸化を確認した.さらにR167Gの54番と315番のどちらのチロシンがリン酸化によるクロマチン集積に必要かを調べるために,二重の変異体(RAD51Y54F/R167GとRAD51R167G/Y315F)を作製して,蛍光抗体法でc-Abl共発現の場合のRAD51の局在を検討した.その結果,R167Gのc-Abl共発現によるクロマチン集積には,RAD51の315番のチロシンのリン酸化が重要であることが判明した.以上の結果から,c-Ablが自身のキナーゼ活性依存性にDNA損傷部位に移行し,BRCA2依存性にDNA損傷部位に移行したRad51のチロシン隣酸化を行い,おそらくはRad51の自己集合あるいはDNA結合を制御することにより,最終的にRad51のDNA損傷部位でのフィラメント形成を促進すると考えられる.今後,DNA損傷によるc-Ablファミリーの活性化と,チロシンキナーゼ活性依存性に起こるDNA損傷部位への集積の機序について,BRCA1とTopBP1の役割に重点をおいて検討すると共に,Rad51の相同組み換えDNA修復能への,分子標的薬剤Glivecの影響について検討する.","subitem_description_type":"Abstract"},{"subitem_description":"c-Abl tyrosine kinase is activated by DNA damage, such as ionizing radiation (IR), in an ATM-dependent manner, and plays important roles in growth arrest and cell death. c-Abl has also been shown to be involved in DNA repair through the phosphorylation of Rad51, a key molecule in homologous recombination repair (HRR). However, it is unclear how c-Abl mechanistically regulates Rad51 functions. In the present study, we show that c-Abl associates and is activated in the chromatin in kinase activity dependent manners. By using self-association defective Rad51 mutants, we further show that c-Abl phosphorylates and stabilizes Rad51 chromatin association in a Tyr-31 5-dependent manner. However, c-Abl cannot restore the defect of the self-association defective mutants in IR-induced nuclear focus formation, suggesting that c-Abl functions the early step of Rad51 chromatin assembly, before self-association-dependent Rad51 nucleoprotein filament formation at DNA damage sites.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:18590286, 研究期間(年度):2006-2007","subitem_description_type":"Other"},{"subitem_description":"出典：「c-AblファミリーのクロマチンにおけるRad51の機能制御の意義」研究成果報告書　課題番号18590286\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050567","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=60115285","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590286/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18590286/185902862007kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-04-19"}],"displaytype":"detail","filename":"CA-PR-YAMAMOTO-K-kaken 2008-9p.pdf","filesize":[{"value":"308.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-YAMAMOTO-K-kaken 2008-9p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44225/files/CA-PR-YAMAMOTO-K-kaken 2008-9p.pdf"},"version_id":"ac070e8c-8400-48a7-962e-a0783a04acfa"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"c-AblファミリーのクロマチンにおけるRad51の機能制御の意義","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"c-AblファミリーのクロマチンにおけるRad51の機能制御の意義"},{"subitem_title":"c-Abl regulates Rad51 chromatin association","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2826"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-04-20"},"publish_date":"2018-04-20","publish_status":"0","recid":"44225","relation_version_is_last":true,"title":["c-AblファミリーのクロマチンにおけるRad51の機能制御の意義"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:24:25.956496+00:00"}