BLM helicase regulates DNA repair by counteracting RAD51 loading at DNA double-strand break sites

J Cell Biol. 2017 Nov 6;216(11):3521-3534. doi: 10.1083/jcb.201703144. Epub 2017 Sep 14.

Abstract

The BLM gene product, BLM, is a RECQ helicase that is involved in DNA replication and repair of DNA double-strand breaks by the homologous recombination (HR) pathway. During HR, BLM has both pro- and anti-recombinogenic activities, either of which may contribute to maintenance of genomic integrity. We find that in cells expressing a mutant version of BRCA1, an essential HR factor, ablation of BLM rescues genomic integrity and cell survival in the presence of DNA double-strand breaks. Improved genomic integrity in these cells is linked to a substantial increase in the stability of RAD51 at DNA double-strand break sites and in the overall efficiency of HR. Ablation of BLM also rescues RAD51 foci and HR in cells lacking BRCA2 or XRCC2. These results indicate that the anti-recombinase activity of BLM is of general importance for normal retention of RAD51 at DNA break sites and regulation of HR.

Publication types

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

MeSH terms

  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • BRCA2 Protein / deficiency
  • BRCA2 Protein / genetics
  • Cell Line, Tumor
  • Cell Survival
  • DNA Breaks, Double-Stranded*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Genomic Instability
  • Genotype
  • Humans
  • Lymphocytes / enzymology*
  • Lymphocytes / pathology
  • Mice, Knockout
  • Mutation
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Phenotype
  • Protein Stability
  • RNA Interference
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism*
  • RecQ Helicases / deficiency
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Recombinational DNA Repair*
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor p53-Binding Protein 1 / deficiency
  • Tumor Suppressor p53-Binding Protein 1 / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Brca1 protein, mouse
  • DNA-Binding Proteins
  • Trp53bp1 protein, mouse
  • Tumor Suppressor Proteins
  • Tumor Suppressor p53-Binding Protein 1
  • XRCC2 protein, human
  • RAD51 protein, human
  • Rad51 Recombinase
  • Rad51 protein, mouse
  • Bloom syndrome protein
  • RecQ Helicases

Associated data

  • GENBANK/S32357
  • GENBANK/A11006