Insight into DNA substrate specificity of PARP1-catalysed DNA poly(ADP-ribosyl)ation

Abstract

This study investigates how PARP1 recognizes and PARylates various DNA duplex substrates with different types and positions of strand breaks. The authors found that PARP1 preferentially attaches ADP-ribose moieties to 3′-terminal phosphate residues at double-strand break ends, influenced by the orientation and spacing of DNA strand breaks on the same molecule. This preference surpasses PARP1 self-PARylation and holds both for purified recombinant PARP1 and HeLa cell extracts, suggesting that in vivo DNA modification by PARP1 strongly depends on DNA break configuration.,