Role of mammalian Mre11 in classical and alternative nonhomologous end joining

被引:270
作者
Xie, Anyong [1 ]
Kwok, Amy
Scully, Ralph
机构
[1] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
STRAND-BREAK REPAIR; CLASS SWITCH RECOMBINATION; DNA-DAMAGE-RESPONSE; V(D)J RECOMBINATION; HISTONE H2AX; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; IONIZING-RADIATION; LENGTH MAINTENANCE;
D O I
10.1038/nsmb.1640
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mammalian Mre11-Rad50-Nbs1 (MRN) complex coordinates double-strand break signaling with repair by homologous recombination and is associated with the H2A.X chromatin response to double-strand breaks, but its role in nonhomologous end joining (NHEJ) is less clear. Here we show that Mre11 promotes efficient NHEJ in both wild-type and Xrcc4(-/-) mouse embryonic stem cells. Depletion of Mre11 reduces the use of microhomology during NHEJ in Xrcc4(+/+) cells and suppresses end resection in Xrcc4(-/-) cells, revealing specific roles for Mre11 in both classical and alternative NHEJ. The NHEJ function of Mre11 is independent of H2A.X. We propose a model in which both enzymatic and scaffolding functions of Mre11 cooperate to support mammalian NHEJ.
引用
收藏
页码:814 / U31
页数:6
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