Mcm8 and Mcm9 Form a Complex that Functions in Homologous Recombination Repair Induced by DNA Interstrand Cross links

被引：108

作者：

Nishimura, Kohei ^{[1
]}

Ishiai, Masamichi ^{[2
]}

Horikawa, Kazuki ^{[1
,3
]}

Fukagawa, Tatsuo ^{[3
,4
]}

Takata, Minoru ^{[2
]}

Takisawa, Haruhiko ^{[5
]}

Kanemaki, Masato T. ^{[1
,3
]}

机构：

[1] Res Org Informat & Syst, Natl Inst Genet, Frontier Res Ctr, Mishima, Shizuoka 4118540, Japan

[2] Kyoto Univ, Ctr Radiat Biol, Dept Late Effects Studies, Sakyo Ku, Kyoto 6068501, Japan

[3] SOKENDAI, Dept Genet, Mishima, Shizuoka 4118540, Japan

[4] Natl Inst Genet, Div Mol Genet, Mishima, Shizuoka 4118540, Japan

[5] Osaka Univ, Grad Sch Sci, Dept Biol Sci, Toyonaka, Osaka 5600043, Japan

来源：

MOLECULAR CELL | 2012年 / 47卷 / 04期

关键词：

FANCONI-ANEMIA PATHWAY; DOUBLE-STRAND BREAKS; PROTEIN FAMILY; THERMOCOCCUS KODAKARENSIS; GENOMIC STABILITY; TUMOR SUPPRESSION; CELL-CYCLE; S-PHASE; PROMOTES; REPLICATION;

D O I：

10.1016/j.molcel.2012.05.047

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 interstrand crosslinks (ICLs) are highly toxic lesions that stall the replication fork to initiate the repair process during the S phase of vertebrates. Proteins involved in Fanconi anemia (FA), nucleotide excision repair (NER), and translesion synthesis (TS) collaboratively lead to homologous recombination (HR) repair. However, it is not understood how ICL-induced HR repair is carried out and completed. Here, we showed that the replicative helicase-related Mm family of proteins, Mcm8 and Mcm9, forms a complex required for HR repair induced by ICLs. Chicken DT40 cells lacking MCM8 or MCM9 are viable but highly sensitive to ICL-inducing agents, and exhibit more chromosome aberrations in the presence of mitomycin C compared with wild-type cells. During ICL repair, Mcm8 and Mcm9 form nuclear foci that partly colocalize with Rad51. Mcm8-9 works downstream of the FA and BRCA2/Rad51 pathways, and is required for HR that promotes sister chromatid exchanges, probably as a hexameric ATPase/helicase.

引用

页码：511 / 522

页数：12

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