Acylpeptide hydrolase is a component of the cellular response to DNA damage

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

[img] PDF - Accepted Version
Restricted to SRO admin only until 24 August 2018.

Download (6MB)

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: 26 Sep 2017 11:20
URI: http://sro.sussex.ac.uk/id/eprint/70195

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
Molecular Characterisation of a Novel Human Tyrosyl DNA PhosphodiesteraseG0206MRC-MEDICAL RESEARCH COUNCILG0901606 145884
Characterisation of the role of oxidised protein hydrolase in the molecular and cellular response to chromosome damageR3H1BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/C516595/1