MCM9 Is Required for Mammalian DNA Mismatch Repair

被引：52

作者：

Traver, Sabine ^{[1
]}

Coulombe, Philippe ^{[1
]}

Peiffer, Isabelle ^{[1
]}

Hutchins, James R. A. ^{[1
]}

Kitzmann, Magali ^{[1
]}

Latreille, Daniel ^{[2
]}

Mechali, Marcel ^{[1
]}

机构：

[1] CNRS, Inst Human Genet, Lab DNA Replicat & Genome Dynam, F-34396 Montpellier, France

[2] CNRS, Inst Human Genet, Lab Gene Regulat, F-34396 Montpellier, France

来源：

MOLECULAR CELL | 2015年 / 59卷 / 05期

基金：

欧洲研究理事会;

关键词：

HOMOLOGOUS RECOMBINATION; CHROMOSOMAL INSTABILITY; GENETIC-RECOMBINATION; HELICASE INTERACTS; POLYMERASE-DELTA; OVARIAN FAILURE; COLON-CANCER; MUTL-ALPHA; STEM-CELLS; REPLICATION;

D O I：

10.1016/j.molcel.2015.07.010

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：

DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects DNA polymerase errors during replication to maintain genomic integrity. In E. coli, the DNA helicase UvrD is implicated in MMR, yet an analogous helicase activity has not been identified in eukaryotes. Here, we show that mammalian MCM9, a protein involved in replication and homologous recombination, forms a complex with MMR initiation proteins (MSH2, MSH3, MLH1, PMS1, and the clamp loader RFC) and is essential for MMR. Mcm9(-/-) cells display microsatellite instability and MMR deficiency. The MCM9 complex has a helicase activity that is required for efficient MMR since wild-type but not helicase-dead MCM9 restores MMR activity in Mcm9(-/-) cells. Moreover, MCM9 loading onto chromatin is MSH2-dependent, and in turn MCM9 stimulates the recruitment of MLH1 to chromatin. Our results reveal a role for MCM9 and its helicase activity in mammalian MMR.

引用

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页码：831 / 839

页数：9

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