Fine-tuning of DNA base excision/strand break repair via acetylation

Abstract

In addition to the key roles of reversible acetylation of histones in chromatin in epigenetic regulation of gene expression, acetylation of nonhistone proteins by histone acetyltransferases (HATs) p300 and CBP is involved in DNA transactions, including repair of base damages and strand breaks. We characterized acetylation of human NEIL1 DNA glycosylase and AP-endonuclease 1 (APE1), which initiate repair of oxidized bases and single-strand breaks (SSBs), respectively. Acetylation induces localized conformation change because of neutralization of the positive charge of specific acetyl-acceptor Lys residues, which are often present in clusters. Acetylation in NEIL1, APE1, and possibly other base excision repair (BER)/SSB repair (SSBR) enzymes by HATs, prebound to chromatin, induces assembly of active repair complexes on the chromatin. In this review, we discuss the roles of acetylation of NEIL1 and APE1 in modulating their activities and complex formation with other proteins for fine-tuning BER in chromatin. Further, the implications of promoter/enhancer-bound acetylated BER protein complexes in the regulation of transcriptional activation, mediated by complex interplay of acetylation and demethylation of histones are discussed.

Keywords: APE1; Acetylation; BER complexes; Base excision repair (BER); DNA base damage; Histone acetyltransferases (HATs); NEIL1.