Format

Send to

Choose Destination
Nucleic Acids Res. 2010 Oct;38(19):6350-62. doi: 10.1093/nar/gkq463. Epub 2010 Jun 4.

PARP1 ADP-ribosylates lysine residues of the core histone tails.

Author information

1
Institute of Veterinary Biochemistry and Molecular Biology, Life Science Zurich Graduate School, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

Abstract

The chromatin-associated enzyme PARP1 has previously been suggested to ADP-ribosylate histones, but the specific ADP-ribose acceptor sites have remained enigmatic. Here, we show that PARP1 covalently ADP-ribosylates the amino-terminal histone tails of all core histones. Using biochemical tools and novel electron transfer dissociation mass spectrometric protocols, we identify for the first time K13 of H2A, K30 of H2B, K27 and K37 of H3, as well as K16 of H4 as ADP-ribose acceptor sites. Multiple explicit water molecular dynamics simulations of the H4 tail peptide into the catalytic cleft of PARP1 indicate that two stable intermolecular salt bridges hold the peptide in an orientation that allows K16 ADP-ribosylation. Consistent with a functional cross-talk between ADP-ribosylation and other histone tail modifications, acetylation of H4K16 inhibits ADP-ribosylation by PARP1. Taken together, our computational and experimental results provide strong evidence that PARP1 modifies important regulatory lysines of the core histone tails.

PMID:
20525793
PMCID:
PMC2965223
DOI:
10.1093/nar/gkq463
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center