DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination

Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):E3495-504. doi: 10.1073/pnas.1507105112. Epub 2015 Jun 22.


Damage repair mechanisms at transcriptionally active sites during the G0/G1 phase are largely unknown. To elucidate these mechanisms, we introduced genome site-specific oxidative DNA damage and determined the role of transcription in repair factor assembly. We find that KU and NBS1 are recruited to damage sites independent of transcription. However, assembly of RPA1, RAD51C, RAD51, and RAD52 at such sites is strictly governed by active transcription and requires both wild-type Cockayne syndrome protein B (CSB) function and the presence of RNA in the G0/G1 phase. We show that the ATPase activity of CSB is indispensable for loading and binding of the recombination factors. CSB counters radiation-induced DNA damage in both cells and zebrafish models. Taken together, our results have uncovered a novel, RNA-based recombination mechanism by which CSB protects genome stability from strand breaks at transcriptionally active sites and may provide insight into the clinical manifestations of Cockayne syndrome.

Keywords: CSB; DNA damage; RNA polymerase II; recombination; transcription.

Publication types

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

MeSH terms

  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism
  • Blotting, Western
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Cockayne Syndrome / genetics
  • Cockayne Syndrome / metabolism
  • Cockayne Syndrome / pathology
  • DNA Damage*
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Repair
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • G1 Phase / genetics
  • HEK293 Cells
  • HeLa Cells
  • Homologous Recombination*
  • Humans
  • Ku Autoantigen
  • Microscopy, Confocal
  • Models, Genetic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Poly-ADP-Ribose Binding Proteins
  • RNA / genetics*
  • RNA / metabolism
  • RNA Interference
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Rad52 DNA Repair and Recombination Protein / genetics
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Replication Protein A / genetics
  • Replication Protein A / metabolism
  • Resting Phase, Cell Cycle / genetics
  • Transcription, Genetic


  • Antigens, Nuclear
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RAD51C protein, human
  • RPA1 protein, human
  • Rad52 DNA Repair and Recombination Protein
  • Replication Protein A
  • RNA
  • Rad51 Recombinase
  • DNA Helicases
  • ERCC6 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Repair Enzymes