PARP1 Binding to DNA Breaks and Hairpins Alters Nucleosome Structure

Resumo

Poly(ADP-ribose)polymerase 1 (PARP1) is involved in the processes of DNA repair, replication, transcription, cell cycle regulation, and apoptosis. Participation of PARP1 in DNA repair is determined by the ability of the enzyme to interact with various damages and noncanonical structures of DNA with consequent polyADP-ribosylation of neighboring proteins. Earlier, for mononucleosomes containing a DNA end recapitulating double-strand DNA break near the nucleosome, it was found that PARP1 induces nucleosome structural changes in the absence of NAD⁺. In the present work, it is reported that PARP1 induces similar structural changes in nucleosomes containing either DNA ends extending from the core by 20 bp or containing hairpins at the DNA ends. In all the cases, PARP1 caused changes in DNA wrapping on the surface of the histone octamer that are accompanied by an increase in the distance between adjacent DNA gyres. These PARP1-mediated changes in the nucleosome structure presumably contribute to chromatin decondensation and facilitate access of repair enzymes to damaged DNA.