CtIP-mediated resection is essential for viability and can operate independently of BRCA1.
CtIP-mediated resection is essential for viability and can operate independently of BRCA1.
复制标题
DOI：
10.1084/jem.20131939
复制
发表时间：
2014-06-02
期刊：
影响因子：
--
通讯作者：
Nussenzweig A
中科院分区：
文献类型：
--
作者：
Polato F;Callen E;Wong N;Faryabi R;Bunting S;Chen HT;Kozak M;Kruhlak MJ;Reczek CR;Lee WH;Ludwig T;Baer R;Feigenbaum L;Jackson S;Nussenzweig A
In contrast to BRCA1, CtIP has indispensable roles in promoting resection and embryonic development. Homologous recombination (HR) is initiated by DNA end resection, a process in which stretches of single-strand DNA (ssDNA) are generated and used for homology search. Factors implicated in resection include nucleases MRE11, EXO1, and DNA2, which process DNA ends into 3′ ssDNA overhangs; helicases such as BLM, which unwind DNA; and other proteins such as BRCA1 and CtIP whose functions remain unclear. CDK-mediated phosphorylation of CtIP on T847 is required to promote resection, whereas CDK-dependent phosphorylation of CtIP-S327 is required for interaction with BRCA1. Here, we provide evidence that CtIP functions independently of BRCA1 in promoting DSB end resection. First, using mouse models expressing S327A or T847A mutant CtIP as a sole species, and B cells deficient in CtIP, we show that loss of the CtIP-BRCA1 interaction does not detectably affect resection, maintenance of genomic stability or viability, whereas T847 is essential for these functions. Second, although loss of 53BP1 rescues the embryonic lethality and HR defects in BRCA1-deficient mice, it does not restore viability or genome integrity in CtIP−/− mice. Third, the increased resection afforded by loss of 53BP1 and the rescue of BRCA1-deficiency depend on CtIP but not EXO1. Finally, the sensitivity of BRCA1-deficient cells to poly ADP ribose polymerase (PARP) inhibition is partially rescued by the phospho-mimicking mutant CtIP (CtIP-T847E). Thus, in contrast to BRCA1, CtIP has indispensable roles in promoting resection and embryonic development.
登录
查看更多内容
影响因子：
16
作者：
Peterson SE;Li Y;Wu-Baer F;Chait BT;Baer R;Yan H;Gottesman ME;Gautier J
通讯作者：
Gautier J
影响因子：
4
作者：
Chapman, J. Ross;Sossick, Alex J.;Jackson, Stephen P.
通讯作者：
Jackson, Stephen P.
由 53BP1-RIF1 和 BRCA1-CtIP 组成的细胞周期依赖性调节回路控制 DNA 修复途径的选择。
影响因子：
16
作者：
Escribano-Diaz, Cristina;Orthwein, Alexandre;Durocher, Daniel
通讯作者：
Durocher, Daniel
人CTIP介导DNA终端切除和双链断裂修复的细胞周期控制。
DOI：
10.1074/jbc.m808906200
发表时间：
2009-04-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huertas P;Jackson SP
通讯作者：
Jackson SP
影响因子：
16.6
作者：
Chandramouly, Gurushankar;Kwok, Amy;Huang, Bin;Willis, Nicholas A.;Xie, Anyong;Scully, Ralph
通讯作者：
Scully, Ralph