• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair.

BRCA1 plays an important role in the homologous recombination (HR)-mediated DNA double-strand break (DSB) repair, but the mechanism is not clear. Here we describe that BRCA1 forms a complex with CtIP and MRN (Mre11/Rad50/Nbs1) in a cell cycle-dependent manner. Significantly, the complex formation, especially the ionizing radiation-enhanced association of BRCA1 with MRN, requires cyclin-dependent kinase activity. CtIP directly interacts with Nbs1. The in vivo association of BRCA1 with MRN is largely dependent on the association of CtIP with the BRCT domains at the C terminus of BRCA1, whereas the N terminus of BRCA1 also contributes to its association with MRN. CtIP, as well as the interaction of BRCA1 with CtIP and MRN, is critical for IR-induced single-stranded DNA formation and cellular resistance to radiation. Consistently, CtIP itself is required for efficient HR-mediated DSB repair, like BRCA1 and MRN. These studies suggest that the complex formation of BRCA1.CtIP.MRN is important for facilitating DSB resection to generate single-stranded DNA that is needed for HR-mediated DSB repair. Because cyclin-dependent kinase is important for establishing IR-enhanced interaction of MRN with BRCA1, we propose that the cell cycle-dependent complex formation of BRCA1, CtIP, and MRN contributes to the activation of HR-mediated DSB repair in the S and G(2) phases of the cell cycle.

Pubmed ID: 18171670


  • Chen L
  • Nievera CJ
  • Lee AY
  • Wu X


The Journal of biological chemistry

Publication Data

March 21, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: CA102361

Mesh Terms

  • BRCA1 Protein
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Cyclin-Dependent Kinases
  • DNA Breaks, Double-Stranded
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • G2 Phase
  • Humans
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Radiation, Ionizing
  • S Phase