The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination

PLoS Genet. 2011 Jul;7(7):e1002148. doi: 10.1371/journal.pgen.1002148. Epub 2011 Jul 14.

Abstract

RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA2 Protein / genetics*
  • Camptothecin / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Chickens
  • Chromosome Aberrations / drug effects
  • Chromosome Aberrations / radiation effects
  • Cisplatin / pharmacology
  • Clone Cells
  • DNA Damage
  • Epistasis, Genetic* / drug effects
  • Epistasis, Genetic* / radiation effects
  • Gamma Rays
  • Gene Conversion / drug effects
  • Gene Conversion / radiation effects
  • Gene Deletion
  • Genetic Loci / genetics
  • Genome / genetics
  • Homologous Recombination* / drug effects
  • Homologous Recombination* / radiation effects
  • Models, Biological
  • Phenotype
  • Phthalazines / pharmacology
  • Piperazines / pharmacology
  • Rad51 Recombinase / deficiency
  • Rad51 Recombinase / genetics*

Substances

  • BRCA2 Protein
  • Phthalazines
  • Piperazines
  • Rad51 Recombinase
  • Cisplatin
  • olaparib
  • Camptothecin