APEH DNAR Accepted version.pdf (6.34 MB)
Acylpeptide hydrolase is a component of the cellular response to DNA damage
journal contribution
posted on 2023-06-09, 07:54 authored by Zhihong Zeng, Stuart L Rulten, Claire Breslin, Anastasia Zlatanou, Victoria Coulthard, Keith CaldecottKeith CaldecottAcylpeptide 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 RepairISSN
1568-7864Publisher
ElsevierExternal DOI
Volume
58Page range
52-61Department 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
2017-09-14First Open Access (FOA) Date
2018-08-24First Compliant Deposit (FCD) Date
2017-09-14Usage metrics
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