Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks

Kohei Nishimura; Masamichi Ishiai; Kazuki Horikawa; Tatsuo Fukagawa; Minoru Takata; Haruhiko Takisawa; Masato T Kanemaki

doi:10.1016/j.molcel.2012.05.047

Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks

Mol Cell. 2012 Aug 24;47(4):511-22. doi: 10.1016/j.molcel.2012.05.047. Epub 2012 Jul 5.

Authors

Kohei Nishimura¹, Masamichi Ishiai, Kazuki Horikawa, Tatsuo Fukagawa, Minoru Takata, Haruhiko Takisawa, Masato T Kanemaki

Affiliation

¹ Center for Frontier Research, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka 411-8540, Japan.

PMID: 22771115
DOI: 10.1016/j.molcel.2012.05.047

Abstract

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 Mcm 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / metabolism
Animals
BRCA2 Protein / genetics
BRCA2 Protein / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Survival / drug effects
Cell Survival / genetics
Cells, Cultured
Chickens
Chromosome Aberrations / drug effects
Cross-Linking Reagents / pharmacology*
DNA / genetics
DNA / metabolism
DNA Helicases / genetics
DNA Helicases / metabolism
DNA Replication / drug effects
DNA Replication / genetics
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Fanconi Anemia / genetics
Fanconi Anemia / metabolism
Homologous Recombination / drug effects
Homologous Recombination / genetics
Mitomycin / pharmacology
Molecular Sequence Data
Recombinational DNA Repair / drug effects*
Recombinational DNA Repair / genetics*
Sister Chromatid Exchange / drug effects
Sister Chromatid Exchange / genetics

Substances

BRCA2 Protein
Cell Cycle Proteins
Cross-Linking Reagents
DNA-Binding Proteins
Mitomycin
DNA
Adenosine Triphosphatases
DNA Helicases

Associated data

GENBANK/AB689140
GENBANK/AB689141