The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation

FEBS Lett. 2017 Jul;591(14):2155-2166. doi: 10.1002/1873-3468.12724. Epub 2017 Jul 4.

Abstract

The protein associated with Werner syndrome (WRN), is involved in DNA repair, checkpoint activation, and telomere maintenance. To better understand the involvement of WRN in double-strand DNA break (DSB) repair, we analyzed the combinatorial role of WRN-1, the Caenorhabditis elegans WRN helicase, in conjunction with EXO-1 and DNA-2 nucleases. We found that WRN-1 cooperates with DNA-2 to resect DSB ends in a pathway acting in parallel to EXO-1. The wrn-1 mutants show an aberrant accumulation of replication protein A (RPA) and RAD-51, and the same pattern of accumulation is also observed in checkpoint-defective strains. We conclude that WRN-1 plays a conserved role in the resection of DSB ends and mediates checkpoint signaling, thereby influencing levels of RPA and RAD-51.

Keywords: checkpoint activation; double-strand DNA break repair; end resection.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / radiation effects
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Checkpoints* / radiation effects
  • DNA Breaks, Double-Stranded*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair* / radiation effects
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Gamma Rays
  • Mutation
  • Rad51 Recombinase / metabolism
  • Replication Protein A / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Replication Protein A
  • Rad51 Recombinase
  • rad-51 protein, C elegans
  • Endodeoxyribonucleases
  • DNA Helicases
  • dna-2 protein, C elegans
  • WRN-1 protein, C elegans