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APEH DNAR Accepted version.pdf (6.34 MB)

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

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posted on 2023-06-09, 07:54 authored by Zhihong Zeng, Stuart L Rulten, Claire Breslin, Anastasia Zlatanou, Victoria Coulthard, Keith CaldecottKeith Caldecott
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.

Funding

Characterisation of the role of oxidised protein hydrolase in the molecular and cellular response to chromosome damage; R3H1; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/C516595/1

Molecular Characterisation of a Novel Human Tyrosyl DNA Phosphodiesterase; G0206; MRC-MEDICAL RESEARCH COUNCIL; G0901606 145884

History

Publication status

  • Published

File Version

  • Accepted version

Journal

DNA Repair

ISSN

1568-7864

Publisher

Elsevier

Volume

58

Page range

52-61

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-09-14

First Open Access (FOA) Date

2018-08-24

First Compliant Deposit (FCD) Date

2017-09-14

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