Acetylation of the histone H3 tail domain regulates base excision repair on higher-order chromatin structures

Abstract

Despite recent evidence suggesting that histone lysine acetylation contributes to base excision repair (BER) in cells, their exact mechanistic role remains unclear. In order to examine the influence of histone acetylation on the initial steps of BER, we assembled nucleosome arrays consisting of homogeneously acetylated histone H3 (H3K18 and H3K27) and measured the repair of a site-specifically positioned 2′-deoxyuridine (dU) residue by uracil DNA glycosylase (UDG) and apurinic/apyrimidinic endonuclease 1 (APE1). We find that H3K18ac and H3K27ac differentially influence the combined activities of UDG/APE1 on compact chromatin, suggesting that acetylated lysine residues on the H3 tail domain play distinct roles in regulating the initial steps of BER. In addition, we show that the effects of H3 tail domain acetylation on UDG/APE1 activity are at the nucleosome level and do not influence higher-order chromatin folding. Overall, these results establish a novel regulatory role for histone H3 acetylation during the initiation of BER on chromatin.

Impact of the nucleosome histone core on the structure and dynamics of DNA containing pyrimidine-pyrimidone (6-4) photoproduct

“…They can be associated to the development of rather persistent states, and most probably to the partial reshaping of the conformational space of the DNA. The role of the histone tails in the recognition of different lesions has been recently highlighted (37)(38)(39)(40), and may be particularly intriguing given the inherent flexibility of the tails and the fundamental signalling role they play in post-translational modifications.…”

Ferroptosis Induction in Multiple Myeloma Cells Triggers DNA Methylation and Histone Modification Changes Associated with Cellular Senescence

“…Regulates the expression of antioxidant genes; recruits DNA repair enzymes to damaged sites; regulates expression of nucleotide excision repair-related genes [53][54][55][56] Cellular senescence H3K18 deacetylation protects cells against mitotic errors and cellular senescence [57] Genome stability Maintains pericentric hetero-chromatin silencing [57] H3K27ac ↓…”

The impact of epigenetic information on genome evolution

“…For instance, the acetylation of histone proteins promotes certain types of DNA repair, and the phosphorylation of a variant of histone H2A or the methylation of histones H4 and H3 stimulates DNA repair in some cases. Indeed, a variety of HPTMs or histone protein variants accompany DNA damage and may facilitate access to damaged DNA by repair proteins [67,68].…”