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MDC1 interacts with Rad51 and facilitates homologous recombination.

Mediator of DNA damage checkpoint protein-1 (MDC1) is a recently identified nuclear protein that participates in DNA-damage sensing and signaling. Here we report that knockdown of MDC1 by RNA interference results in cellular hypersensitivity to the DNA cross-linking agent mitomycin C and ionizing radiation and in impaired homology-mediated repair of double-strand breaks in DNA. MDC1 forms a complex with Rad51 through a direct interaction with the forkhead-associated domain of MDC1, not the BRCA1 C-terminal domain. Depletion of MDC1 results in impaired formation of Rad51 ionizing radiation-induced foci, reduced amounts of nuclear and chromatin-bound Rad51, and a corresponding increase in Rad51 protein degradation. Together, our findings suggest that MDC1 functions in Rad51-mediated homologous recombination by retaining Rad51 in chromatin.

Pubmed ID: 16186822

Authors

  • Zhang J
  • Ma Z
  • Treszezamsky A
  • Powell SN

Journal

Nature structural & molecular biology

Publication Data

October 5, 2005

Associated Grants

  • Agency: NCI NIH HHS, Id: CA107640

Mesh Terms

  • BRCA1 Protein
  • Cell Cycle
  • Cell Nucleus
  • Chromatin
  • DNA Repair
  • DNA-Binding Proteins
  • Enzyme Stability
  • Gene Silencing
  • Humans
  • Nuclear Proteins
  • Rad51 Recombinase
  • Radiation Tolerance
  • Radiation, Ionizing
  • Recombination, Genetic
  • Trans-Activators