Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김현석 | - |
dc.date.accessioned | 2016-08-28T10:08:24Z | - |
dc.date.available | 2016-08-28T10:08:24Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.other | OAK-10378 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/223971 | - |
dc.description.abstract | Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and is a murine tumor suppressor. We show that SIRT2 directs replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication arrest. SIRT2 deficiency results in replication stress sensitivity, impairment in recovery from replication arrest, spontaneous accumulation of replication protein A to foci and chromatin, and a G2/M checkpoint deficit. SIRT2 interacts with and deacetylates CDK9 at lysine 48 in response to replication stress in a manner that is partially dependent on ataxia telangiectasia and Rad3 related (ATR) but not cyclin T or K, thereby stimulating CDK9 kinase activity and promoting recovery from replication arrest. Moreover, wild-type, but not acetylated CDK9, alleviates the replication stress response impairment of SIRT2 deficiency. Collectively, our results define a function for SIRT2 in regulating checkpoint pathways that respond to replication stress through deacetylation of CDK9, providing insight into how SIRT2 maintains genome integrity and a unique mechanism by which SIRT2 may function, at least in part, as a tumor suppressor protein. | - |
dc.language | English | - |
dc.title | SIRT2 directs the replication stress response through CDK9 deacetylation | - |
dc.type | Article | - |
dc.relation.issue | 33 | - |
dc.relation.volume | 110 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 13546 | - |
dc.relation.lastpage | 13551 | - |
dc.relation.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.identifier.doi | 10.1073/pnas.1301463110 | - |
dc.identifier.wosid | WOS:000323069200074 | - |
dc.identifier.scopusid | 2-s2.0-84882418252 | - |
dc.author.google | Zhang H. | - |
dc.author.google | Park S.-H. | - |
dc.author.google | Pantazides B.G. | - |
dc.author.google | Karpiuk O. | - |
dc.author.google | Warren M.D. | - |
dc.author.google | Hardy C.W. | - |
dc.author.google | Duong D.M. | - |
dc.author.google | Park S.-J. | - |
dc.author.google | Kim H.-S. | - |
dc.author.google | Vassilopoulos A. | - |
dc.author.google | Seyfried N.T. | - |
dc.author.google | Johnsen S.A. | - |
dc.author.google | Gius D. | - |
dc.author.google | Yu D.S. | - |
dc.contributor.scopusid | 김현석(57191717681) | - |
dc.date.modifydate | 20230201113042 | - |