PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis

Curr Opin Struct Biol. 2013 Feb;23(1):134-43. doi: 10.1016/ Epub 2013 Jan 16.


Poly(ADP-ribose) polymerase 1 (PARP-1) regulates gene transcription, cell death signaling, and DNA repair through production of the posttranslational modification poly(ADP-ribose). During the cellular response to genotoxic stress PARP-1 rapidly associates with DNA damage, which robustly stimulates poly(ADP-ribose) production over a low basal level of PARP-1 activity. DNA damage-dependent PARP-1 activity is central to understanding PARP-1 biological function, but structural insights into the mechanisms underlying this mode of regulation have remained elusive, in part due to the highly modular six-domain architecture of PARP-1. Recent structural studies have illustrated how PARP-1 uses specialized zinc fingers to detect DNA breaks through sequence-independent interaction with exposed nucleotide bases, a common feature of damaged and abnormal DNA structures. The mechanism of coupling DNA damage detection to elevated poly(ADP-ribose) production has been elucidated based on a crystal structure of the essential domains of PARP-1 in complex with a DNA strand break. The multiple domains of PARP-1 collapse onto damaged DNA, forming a network of interdomain contacts that introduce destabilizing alterations in the catalytic domain leading to an enhanced rate of poly(ADP-ribose) production.

Publication types

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

MeSH terms

  • Catalysis
  • DNA / genetics*
  • DNA / metabolism
  • DNA Damage*
  • Humans
  • Poly Adenosine Diphosphate Ribose / genetics*
  • Poly(ADP-ribose) Polymerases / chemistry*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Zinc Fingers


  • Poly Adenosine Diphosphate Ribose
  • DNA
  • Poly(ADP-ribose) Polymerases