Journal article
Site-specific Acetylation of Histone H3 Decreases Polymerase β Activity on Nucleosome Core Particles in Vitro
The Journal of biological chemistry, Vol.291(21), pp.11434-11445
05/20/2016
Handle:
https://hdl.handle.net/2376/108340
PMCID: PMC4900286
PMID: 27033702
Abstract
Histone posttranslational modifications have been associated with changes in chromatin structure necessary for transcription, replication, and DNA repair. Acetylation is one of the most studied and best characterized histone posttranslational modifications, but it is not known if histone acetylation modulates base excision repair of DNA lesions in chromatin. To address this question, we generated nucleosome core particles (NCPs) containing site-specifically acetylated H3K14 or H3K56 and measured repair of uracil and single-nucleotide gaps. We find that H3K56Ac and H3K14Ac do not significantly contribute to removal of uracils by uracil DNA glycosylase regardless of the translational or rotational position of the lesions within NCPs. In repair of single-nucleotide gaps, however, the presence of H3K56Ac or H3K14Ac in NCPs decreases the gap-filling activity of DNA polymerase β near the dyad center, with H3K14Ac exhibiting stronger inhibition. To a lesser extent, H3K56Ac induces a similar effect near the DNA ends. Moreover, using restriction enzyme accessibility, we detect no changes in NCP structure or dynamics between H3K14Ac-NCPs and WT-NCPs containing single-nucleotide gaps. Thus, acetylation at H3K56 and H3K14 in nucleosomes may promote alternative gap-filling pathways by inhibiting DNA polymerase β activity.
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Details
- Title
- Site-specific Acetylation of Histone H3 Decreases Polymerase β Activity on Nucleosome Core Particles in Vitro
- Creators
- Yesenia Rodriguez - From Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520John M Hinz - From Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520Marian F Laughery - From Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520John J Wyrick - From Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520Michael J Smerdon - From Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520 smerdon@wsu.edu
- Publication Details
- The Journal of biological chemistry, Vol.291(21), pp.11434-11445
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- T32 GM008336 / NIGMS NIH HHS R01 ES004106 / NIEHS NIH HHS R37 ES002614 / NIEHS NIH HHS R21 ES020955 / NIEHS NIH HHS R01 ES002614 / NIEHS NIH HHS
- Identifiers
- 99900547441701842
- Language
- English
- Resource Type
- Journal article