Protein ADP-ribosylation and the cellular response to DNA strand breaks

DNA Repair (Amst). 2014 Jul:19:108-13. doi: 10.1016/j.dnarep.2014.03.021. Epub 2014 Apr 20.

Abstract

DNA strand breaks arise continuously in cells and can lead to chromosome rearrangements and genome instability or cell death. The commonest DNA breaks are DNA single-strand breaks, which arise at a frequency of tens-of-thousands per cell each day and which can block the progression of RNA/DNA polymerases and disrupt gene transcription and genome duplication. If not rapidly repaired, SSBs can be converted into DNA double-strand breaks (DSBs) during genome duplication, eliciting a complex series of DNA damage responses that attempt to protect cells from irreversible replication fork collapse. DSBs are the most cytotoxic and clastogenic type of DNA breaks, and can also arise independently of DNA replication, albeit at a frequency several orders of magnitude lower than SSBs. Here, I discuss the evidence that DNA single- and double -strand break repair pathways, and cellular tolerance mechanisms for protecting replication forks during genome duplication, utilize signalling by protein ADP-ribosyltransferases to protect cells from the harmful impact of DNA strand breakage.

Keywords: Base excision repair; DNA double-strand break; DNA single-strand break; Homologous recombination; Non-homologous end-joining; Poly(ADP-ribose) polymerase; Single-strand break repair.

Publication types

  • Review

MeSH terms

  • DNA Breaks, Double-Stranded*
  • DNA Breaks, Single-Stranded*
  • DNA Damage / genetics
  • DNA End-Joining Repair / genetics
  • DNA Repair / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Genomic Instability
  • Homologous Recombination*
  • Poly(ADP-ribose) Polymerases / genetics*

Substances

  • DNA-Binding Proteins
  • Poly(ADP-ribose) Polymerases