{"id":2876,"date":"2019-12-31T06:44:33","date_gmt":"2019-12-30T21:44:33","guid":{"rendered":"https:\/\/www.igakuken.or.jp\/genome?post_type=new_publication&#038;p=2876"},"modified":"2019-12-31T06:44:33","modified_gmt":"2019-12-30T21:44:33","slug":"e-life%e8%aa%8c%e3%81%ab%e6%96%b0%e3%81%97%e3%81%84%e8%ab%96%e6%96%87%e3%81%8caccept%e3%81%95%e3%82%8c%e3%81%be%e3%81%97%e3%81%9f%e3%80%82","status":"publish","type":"new_publication","link":"https:\/\/www.igakuken.or.jp\/genome\/?new_publication=e-life%e8%aa%8c%e3%81%ab%e6%96%b0%e3%81%97%e3%81%84%e8%ab%96%e6%96%87%e3%81%8caccept%e3%81%95%e3%82%8c%e3%81%be%e3%81%97%e3%81%9f%e3%80%82","title":{"rendered":"E-life\u8a8c\u306b\u65b0\u3057\u3044\u8ad6\u6587\u304caccept\u3055\u308c\u307e\u3057\u305f\u3002"},"content":{"rendered":"<p>2019\u5e74(\u4ee4\u548c\u5143\u5e74)12\u670831\u65e5\u3000E-life\u8a8c\u306b\u65b0\u3057\u3044\u8ad6\u6587\u304c\u63a1\u629e\u3055\u308c\u307e\u3057\u305f\u3002<\/p>\n<p>Title\uff1aCdc7 activates replication checkpoint by phosphorylating the Chk1 binding domain of Claspin in human cells<\/p>\n<p>Authors\uff1aChi-Chun Yang, Hiroyuki Kato, Mayumi Shindo and Hisao Masai*<\/p>\n<p>Abstract\uff1aReplication checkpoint is essential for maintaining genome integrity in response to various replication stresses as well as during the normal growth. The evolutionally conserved ATR-Claspin-Chk1 pathway is induced during replication checkpoint activation. Cdc7 kinase, required for initiation of DNA replication at replication origins, has been implicated in checkpoint activation but how it is involved in this pathway has not been known. Here, we show that Cdc7 is required for Claspin-Chk1 interaction in human cancer cells by phosphorylating CKBD (Chk1-binding-domain) of Claspin. The residual Chk1 activation in Cdc7-depleted cells is lost upon further depletion of casein kinase1\u00a0(CK1\u03b31), previously reported to phosphorylate CKBD. Thus, Cdc7, in conjunction with CK1\u03b31, facilitates the interaction between Claspin and Chk1 through phosphorylating CKBD. We also show that, whereas Cdc7 is predominantly responsible for CKBD phosphorylation in cancer cells, CK1\u03b31plays a major role in non-cancer cells, providing rationale for targeting Cdc7 for cancer cell-specific cell killing.<\/p>\n<p>\u672c\u8ad6\u6587\u3067\u306f\u3001\u30d2\u30c8Cdc7\u30ad\u30ca\u30fc\u30bc\u304c\u8907\u88fd\u30c1\u30a7\u30c3\u30af\u30dd\u30a4\u30f3\u30c8\u30a2\u30c0\u30d7\u30bf\u30fc\u30bf\u30f3\u30d1\u30af\u8cea\u3067\u3042\u308bClaspin\u306e\u30ea\u30f3\u9178\u5316\u3092\u4ecb\u3057\u3066DNA\u8907\u88fd\u30c1\u30a7\u30c3\u30af\u30dd\u30a4\u30f3\u30c8\u3092\u6d3b\u6027\u5316\u3059\u308b\u30e1\u30ab\u30cb\u30ba\u30e0\u3092\u89e3\u660e\u3057\u307e\u3057\u305f\u3002\u3055\u3089\u306bCdc7\u306f\u3001\u304c\u3093\u7d30\u80de\u306b\u304a\u3044\u3066\u7279\u7570\u7684\u306b\u8907\u88fd\u30c1\u30a7\u30c3\u30af\u30dd\u30a4\u30f3\u30c8\u306e\u6d3b\u6027\u5316\u306b\u95a2\u4e0e\u3059\u308b\u306e\u306b\u5bfe\u3057\u3066\u3001\u6b63\u5e38\u7d30\u80de\u3067\u306fCK1\u03b31\u30ad\u30ca\u30fc\u30bc\u304c\u4e3b\u8981\u306a\u5f79\u5272\u3092\u679c\u305f\u3059\u3053\u3068\u3092\u898b\u51fa\u3057\u307e\u3057\u305f\u3002\u3053\u308c\u3089\u306e\u767a\u898b\u306f\u3001\u304c\u3093\u7d30\u80de\u306f\u6b63\u5e38\u7d30\u80de\u3068\u7570\u306a\u308b\u5206\u5b50\u3092\u7528\u3044\u3066\u8907\u88fd\u30b9\u30c8\u30ec\u30b9\u3092\u5236\u5fa1\u3057\u3066\u3044\u308b\u3053\u3068\u3092\u793a\u3057\u3001\u304c\u3093\u7d30\u80de\u7279\u7570\u7684\u306a\u5897\u6b96\u5236\u5fa1\u3001\u7d30\u80de\u6b7b\u8a98\u5c0e\u306e\u305f\u3081\u306e\u6226\u7565\u306e\u53ef\u80fd\u6027\u3092\u793a\u5506\u3057\u307e\u3059\u3002<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"featured_media":0,"template":"","_links":{"self":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/new_publication\/2876"}],"collection":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/new_publication"}],"about":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=\/wp\/v2\/types\/new_publication"}],"wp:attachment":[{"href":"https:\/\/www.igakuken.or.jp\/genome\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2876"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}