Moonlighting at replication forks - a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51

FEBS Lett. 2017 Apr;591(8):1083-1100. doi: 10.1002/1873-3468.12556. Epub 2017 Jan 30.

Abstract

Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Emerging evidence has linked homologous recombination (HR) proteins RAD51, BRCA1 and BRCA2 to the stability of nascent DNA. This function appears to be distinct from double-strand break (DSB) repair and is in part due to the prevention of MRE11-mediated degradation of nascent DNA at stalled forks. The role of RAD51 in fork protection resembles the activity described for its prokaryotic orthologue RecA, which prevents nuclease-mediated degradation of DNA and promotes replication fork restart in cells challenged by DNA-damaging agents. Here, we examine the mechanistic aspects of HR-mediated fork protection, addressing the crosstalk between HR and replication proteins.

Keywords: DNA recombination; DNA replication; genome stability.

Publication types

  • Review

MeSH terms

  • Acid Anhydride Hydrolases
  • Animals
  • BRCA1 Protein / metabolism*
  • BRCA2 Protein / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Chromosomal Instability
  • DNA Breaks
  • DNA Repair Enzymes / chemistry
  • DNA Repair Enzymes / metabolism
  • DNA Replication*
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Homologous Recombination*
  • Humans
  • MRE11 Homologue Protein
  • Models, Biological*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Protein Multimerization
  • Rad51 Recombinase / metabolism*
  • Replication Protein A / antagonists & inhibitors
  • Replication Protein A / chemistry
  • Replication Protein A / metabolism

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MRE11 protein, human
  • NBN protein, human
  • Nuclear Proteins
  • Replication Protein A
  • RAD51 protein, human
  • Rad51 Recombinase
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • RAD50 protein, human
  • DNA Repair Enzymes