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

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.

authors

• Sczepanski, Jonathan

published proceedings

• Sci Rep

altmetric score

• 3.5

author list (cited authors)

• Banerjee, D. R., Deckard, C. E., Zeng, Y. u., & Sczepanski, J. T.

citation count

• 13

complete list of authors

• Banerjee, Deb Ranjan||Deckard, Charles E||Zeng, Yu||Sczepanski, Jonathan T

publication date

• January 2019

publisher

• Springer Nature  Publisher

published in

• Scientific Reports  Journal

keywords

• Acetylation
• Chromatin
• DNA Repair
• DNA-(Apurinic Or Apyrimidinic Site) Lyase
• Histones
• Humans
• Models, Molecular
• Molecular Conformation
• Nucleosomes
• Protein Domains
• Structure-Activity Relationship
• Uracil-dna Glycosidase

Digital Object Identifier (DOI)

• 10.1038/s41598-019-52340-0

start page

• 15972

volume

• 9

issue

• 1

URL

• http://dx.doi.org/10.1038/s41598-019-52340-0