A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination

Mol Cell. 2007 Mar 9;25(5):663-75. doi: 10.1016/j.molcel.2007.01.029.


The ubiquitin (Ub)-conjugating enzyme Ubc13 is implicated in Rad6/Rad18-dependent postreplication repair (PRR) in budding yeast, but its function in vertebrates is not known. We show here that disruption or siRNA depletion of UBC13 in chicken DT40 or human cells confers severe growth defects due to chromosome instability, and hypersensitivity to both UV and ionizing radiation, consistent with a conserved role for Ubc13 in PRR. Remarkably, Ubc13-deficient cells are also compromised for DNA double-strand break (DSB) repair by homologous recombination (HR). Recruitment and activation of the E3 Ub ligase function of BRCA1 and the subsequent formation of the Rad51 nucleoprotein filament at DSBs are abolished in Ubc13-deficient cells. Furthermore, generation of ssDNA/RPA complexes at DSBs is severely attenuated in the absence of Ubc13. These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of HR at the level of DSB processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / radiation effects
  • Chickens
  • Chromosomes / drug effects
  • Chromosomes / radiation effects
  • DNA / metabolism
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • Enzyme Activation / drug effects
  • Enzyme Activation / radiation effects
  • Exons / genetics
  • Gene Targeting
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Infrared Rays
  • Models, Genetic
  • Mutagens / toxicity
  • Rad51 Recombinase / metabolism
  • Recombination, Genetic* / drug effects
  • Recombination, Genetic* / radiation effects
  • Replication Protein A / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes / deficiency
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Ultraviolet Rays


  • BRCA1 Protein
  • Histones
  • Mutagens
  • Replication Protein A
  • Ubiquitin
  • DNA
  • UBE2N protein, human
  • Ubiquitin-Conjugating Enzymes
  • Rad51 Recombinase