Covalent Modification of Bromodomain Proteins by Peptides Containing a DNA Damage-Induced, Histone Post-Translational Modification.

ABSTRACT: An electrophilic 5-methylene-2-pyrrolone modification (K_MP ) is produced at lysine residues of histone proteins in nucleosome core particles upon reaction with a commonly formed DNA lesion (C4-AP). The nonenzymatic K_MP modification is also generated in the histones of HeLa cells treated with the antitumor agent, bleomycin that oxidizes DNA and forms C4-AP. This nonenzymatic covalent histone modification has the same charge as the N-acetyllysine (K_Ac ) modification but is more electrophilic. In this study we show that K_MP -containing histone peptides are recognized by, and covalently modify bromodomain proteins that are K_Ac readers. Distinct selectivity preferences for covalent bromodomain modification are observed following incubation

SUBMITTER: Jacinto MP 

PROVIDER: S-EPMC9675715 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature