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.


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


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

Associated data

  • GENBANK/AB689140
  • GENBANK/AB689141