title: Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks.
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.
authors: Center for Frontier Research, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
authors: Kohei
authors: K
authors: Nishimura
authors: Masamichi
authors: M
authors: Ishiai
authors: Kazuki
authors: K
authors: Horikawa
authors: Tatsuo
authors: T
authors: Fukagawa
authors: Minoru
authors: M
authors: Takata
authors: Haruhiko
authors: H
authors: Takisawa
authors: Masato T
authors: MT
authors: Kanemaki
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens; D002869:Chromosome Aberrations / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination / Q000187:drug effects / Q000235:genetics; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D059767:Recombinational DNA Repair / Q000187:drug effects* / Q000235:genetics*; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D016685:Mitomycin; D004247:DNA; D000251:Adenosine Triphosphatases; D004265:DNA Helicases