Histone Deacetylase 1 Inhibition by Peptides Containing a DNA Damage-Induced, Nonenzymatic, Histone Covalent Modification.

ABSTRACT: Treatment of HeLa cells with the DNA damaging agent, bleomycin (BLM), results in the formation of a nonenzymatic 5-methylene-2-pyrrolone histone covalent modification on lysine residues (K_MP). K_MP is much more electrophilic than other N-acyllysine covalent modifications and post-translational modifications, including N-acetyllysine (K_Ac). Using histone peptides containing K_MP, we show that this modification inhibits the class I histone deacetylase, HDAC1, by reacting with a conserved cysteine (C261) located near the active site. HDAC1 is inhibited by histone peptides whose corresponding N-acetylated sequences are known deacetylation substrates, but not one containing a scrambled sequence. The HDAC1 inhibitor, trichostatin A,

SUBMITTER: Jacinto MP 

PROVIDER: S-EPMC10124317 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature