Rapid Detection and Signaling of DNA Damage by PARP-1

Trends Biochem Sci. 2021 Sep;46(9):744-757. doi: 10.1016/j.tibs.2021.01.014. Epub 2021 Mar 3.


Poly(ADP-ribosyl) polymerase-1 (PARP-1) is an abundant ADP-ribosyl transferase that regulates various biological processes. PARP-1 is widely recognized as a first-line responder molecule in DNA damage response (DDR). Here, we review the full cycle of detecting DNA damage by PARP-1, PARP-1 activation upon DNA binding, and PARP-1 release from a DNA break. We also discuss the allosteric consequence upon binding of PARP inhibitors (PARPi) and the opportunity to tune its release from a DNA break. It is now possible to harness this new understanding to design novel PARPi for treating diseases where cell toxicity caused by PARP-1 'trapping' on DNA is either the desired consequence or entirely counterproductive.

Keywords: DNA damage response; PARPi; PARylation; poly(ADP-ribose) glycohydrolase.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biological Phenomena*
  • DNA Damage
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Signal Transduction


  • Poly(ADP-ribose) Polymerase Inhibitors