Enhanced transcription activity of histone acetyltransferase HBO1 after genotoxic stress

Enhanced transcription activity of histone acetyltransferase HBO1 after genotoxic stress

Chromatin remodeling is induced at sites of DNA damage as part of the damage response to allow DNA repair protein accumulation and stability of function. Histone posttranslational modifications are required to orchestrate DNA damage response, and ubiquitination of histone H2A-K15 at DNA double-stran...

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Bibliographic Details
Published in:Gene reports Vol. 21; p. 100815
Main Authors: Sekine, Shiryu, Sekiguchi, Miyu, Matsushita, Nobuko
Format: Journal Article
Language:English
Published: Elsevier Inc 01-12-2020
Subjects:
Genotoxic stress
HBO1
MYST family
ATM
MYST family
Genotoxic stress
HBO1
ATR
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Summary:Chromatin remodeling is induced at sites of DNA damage as part of the damage response to allow DNA repair protein accumulation and stability of function. Histone posttranslational modifications are required to orchestrate DNA damage response, and ubiquitination of histone H2A-K15 at DNA double-strand break sites is involved in the recruitment of DNA repair protein 53BP1 to DNA damage sites. Acetylation of histone H4K16 promotes homologous recombination repair by inducing dissociation of 53BP1, while deacetylation inhibits the homologous recombination repair by promoting accumulation of 53BP1 at DNA damage sites. Chromatin remodeling is indispensable for accumulation of numerous DNA damage repair proteins and their subsequent dissociation, and we investigated the possibility of new DNA damage response pathway. In this study, we used qPCR, western blotting and survival assays to demonstrate that genotoxic stress, both biochemical and radiological, specifically upregulated the expression of histone acetyltransferase binding to ORC (HBO1) protein in the histone acetyltransferase MYST family, which colocalized with the DNA damage response protein, Fanconi anemia group D2 (FANCD2). HBO1 expression was upregulated via phosphoinositide-3-kinase-related kinase protein, which plays a crucial role as a DNA damage response signal. These results suggest that HBO1induced by genotoxic stress has a critical role in DNA damage responses. •HBO1 mRNA expression was enhanced after genotoxic stress.•Genotoxic stress did not increase other MYST family protein expression.•HBO1 depletion resulted in hypersensitivity to genotoxic stress.
ISSN:2452-0144
2452-0144
DOI:10.1016/j.genrep.2020.100815