Poly-ADP ribosylation in DNA damage response and cancer therapy

Mutat Res Rev Mutat Res. 2019 Apr-Jun:780:82-91. doi: 10.1016/j.mrrev.2017.09.004. Epub 2017 Sep 20.

Abstract

Poly(ADP-ribosyl)ation (aka PARylation) is a unique protein post-translational modification (PTM) first described over 50 years ago. PARylation regulates a number of biological processes including chromatin remodeling, the DNA damage response (DDR), transcription, apoptosis, and mitosis. The subsequent discovery of poly(ADP-ribose) polymerase-1 (PARP-1) catalyzing DNA-dependent PARylation spearheaded the field of DDR. The expanding knowledge about the poly ADP-ribose (PAR) recognition domains prompted the discovery of novel DDR factors and revealed crosstalk with other protein PTMs including phosphorylation, ubiquitination, methylation and acetylation. In this review, we highlight the current knowledge on PAR-regulated DDR, PAR recognition domain, and PARP inhibition in cancer therapy.

Keywords: BRCT domain; DNA damage response; De-PARylation; PAR recognition domain; PARP inhibitor; PARP inhibitor resistance; PARylation; Poly(ADP-ribosyl)ation; Poly(ADP-ribosyl)lation polymerase.

Publication types

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

MeSH terms

  • Animals
  • DNA Damage / drug effects
  • DNA Damage / genetics*
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Poly ADP Ribosylation / drug effects
  • Poly ADP Ribosylation / genetics*
  • Poly Adenosine Diphosphate Ribose / genetics*
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerases / genetics

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases