Zeng, Zhihong, Rulten, Stuart L, Breslin, Claire, Zlatanou, Anastasia, Coulthard, Victoria and Caldecott, Keith (2017) Acylpeptide hydrolase is a component of the cellular response to DNA damage. DNA Repair, 58. pp. 52-61. ISSN 1568-7864

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Abstract

Acylpeptide hydrolase (APEH) deacetylates N-alpha-acetylated peptides and selectively degrades oxidized proteins, but the biochemical pathways that are regulated by this protease are unknown. Here, we identify APEH as a component of the cellular response to DNA damage. Although APEH is primarily localised in the cytoplasm, we show that a sub-fraction of this enzyme is sequestered at sites of nuclear damage following UVA irradiation or following oxidative stress. We show that localization of APEH at sites of nuclear damage is mediated by direct interaction with XRCC1, a scaffold protein that accelerates the repair of DNA single-strand breaks. We show that APEH interacts with the amino-terminal domain of XRCC1, and that APEH facilitates both single-strand break repair and cell survival following exposure to H2O2 in human cells. These data identify APEH as a novel proteolytic component of the DNA damage response.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups:	Genome Damage and Stability Centre
Subjects:	Q Science > Q Science (General)
Depositing User:	Sarah Frances
Date Deposited:	14 Sep 2017 13:55
Last Modified:	02 Jul 2019 14:47
URI:	http://sro.sussex.ac.uk/id/eprint/70195

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