MDC1 interacts with Rad51 and facilitates homologous recombination

Nat Struct Mol Biol. 2005 Oct;12(10):902-9. doi: 10.1038/nsmb991. Epub 2005 Sep 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • BRCA1 Protein
  • Chromatin
  • DNA-Binding Proteins
  • MDC1 protein, human
  • Nuclear Proteins
  • Trans-Activators
  • RAD51 protein, human
  • Rad51 Recombinase