RPA and RAD51: fork reversal, fork protection, and genome stability

Nat Struct Mol Biol. 2018 Jun;25(6):446-453. doi: 10.1038/s41594-018-0075-z. Epub 2018 May 28.


Replication protein A (RPA) and RAD51 are DNA-binding proteins that help maintain genome stability during DNA replication. These proteins regulate nucleases, helicases, DNA translocases, and signaling proteins to control replication, repair, recombination, and the DNA damage response. Their different DNA-binding mechanisms, enzymatic activities, and binding partners provide unique functionalities that cooperate to ensure that the appropriate activities are deployed at the right time to overcome replication challenges. Here we review and discuss the latest discoveries of the mechanisms by which these proteins work to preserve genome stability, with a focus on their actions in fork reversal and fork protection.

Publication types

  • Review

MeSH terms

  • DNA Breaks, Double-Stranded
  • DNA Replication*
  • Genomic Instability*
  • Humans
  • Protein Conformation
  • Rad51 Recombinase / chemistry
  • Rad51 Recombinase / physiology*
  • Replication Protein A / chemistry
  • Replication Protein A / physiology*


  • Replication Protein A
  • RAD51 protein, human
  • Rad51 Recombinase