{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T21:09:32Z","timestamp":1777928972959,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumour Biol."],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>In cholestasis, increases in bile acid levels result in the generation of reactive oxygen species and the induction of DNA damage and mutation. It is believed that bile acid accumulation is associated with liver tumorigenesis. However, the mechanism that underpins this phenomenon remains to be elucidated. Mcl-1, which is overexpressed in hepatic cells, is a pro-survival member of the Bcl-2 family. In this study, we observed that Mcl-1 potently suppresses the repair of bile acid\u2013induced abasic (apurinic\/apyrimidinic) sites in DNA lesions. Upon exposure of hepatic cells to glycochenodeoxycholate, one of the major conjugated human bile acids, we observed an increase in AP site accumulation along with induction of poly(ADP-ribose) polymerase and XRCC1 ( X-Ray Repair Cross Complementing 1). In addition, accumulation of Mcl-1 was observed in the nuclei of QGY-7703 cells in response to glycochenodeoxycholate stimulation. Knockdown of endogenous Mcl-1 by RNA interference significantly accelerated the repair of DNA lesions in glycochenodeoxycholate-treated cells. However, unlike XRCC1, poly(ADP-ribose) polymerase was induced following Mcl-1 knockdown. Conversely, poly(ADP-ribose) polymerase suppression was observed following glycochenodeoxycholate treatment of cells overexpressing Mcl-1. Moreover, AP-site counting analyses revealed that DNA repair activity was enhanced in cells overexpressing poly(ADP-ribose) polymerase under glycochenodeoxycholate stress conditions. It is well known that poly(ADP-ribose) polymerase plays a crucial role in the base excision repair pathway. Thus, our findings suggest that Mcl-1 suppresses base excision repair by inhibiting poly(ADP-ribose) polymerase induction following glycochenodeoxycholate-induced DNA damage. These results potentially explain how bile acid accumulation results in genetic instability and carcinogenesis.<\/jats:p>","DOI":"10.1177\/1010428317712102","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T13:41:42Z","timestamp":1499780502000},"page":"101042831771210","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mcl-1 suppresses abasic site repair following bile acid\u2013induced hepatic cellular DNA damage"],"prefix":"10.1177","volume":"39","author":[{"given":"Haiyang","family":"Yu","sequence":"first","affiliation":[{"name":"Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Fifth Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck Research Laboratory, Kenilworth, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoying","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingmei","family":"Liao","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zanxian","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiande","family":"Liao","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University, Changsha, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,7,6]]},"reference":[{"key":"bibr1-1010428317712102","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.52.0010"},{"key":"bibr2-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1007\/s00534-006-1125-1"},{"key":"bibr3-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2015.04.003"},{"key":"bibr4-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2014.05.021"},{"key":"bibr5-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1089\/15230860152543014"},{"key":"bibr6-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012583"},{"key":"bibr7-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2003.09.012"},{"key":"bibr8-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-11-0477"},{"key":"bibr9-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.38.23970"},{"key":"bibr10-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708345200"},{"key":"bibr11-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22664"},{"key":"bibr12-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3516"},{"key":"bibr13-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1200927"},{"key":"bibr14-1010428317712102","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.14.12354"},{"key":"bibr15-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-44"},{"key":"bibr16-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.56"},{"key":"bibr17-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-016-1614-7"},{"key":"bibr18-1010428317712102","first-page":"572738","author":"Jiang C","year":"2015","journal-title":"Biomed Res Int"},{"key":"bibr19-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24376"},{"key":"bibr20-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.04.017"},{"key":"bibr21-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041596"},{"key":"bibr22-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1594-1"},{"key":"bibr23-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1038\/srep31538"},{"key":"bibr24-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.382"},{"key":"bibr25-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"bibr26-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw015"},{"key":"bibr27-1010428317712102","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.01.017"}],"container-title":["Tumor Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1010428317712102","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1010428317712102","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1010428317712102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:25:43Z","timestamp":1777677943000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.1177\/1010428317712102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1177\/1010428317712102"],"URL":"https:\/\/doi.org\/10.1177\/1010428317712102","relation":{},"ISSN":["1010-4283","1423-0380"],"issn-type":[{"value":"1010-4283","type":"print"},{"value":"1423-0380","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]}}}