Acylpeptide hydrolase is a component of the cellular response to DNA damage
| Autor: | Claire Breslin, Zhihong Zeng, Victoria Coulthard, Anastasia Zlatanou, Stuart L. Rulten, Keith W. Caldecott |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Scaffold protein DNA Repair DNA repair DNA damage Biology Q1 Biochemistry 03 medical and health sciences XRCC1 chemistry.chemical_compound 0302 clinical medicine Humans Protein Interaction Domains and Motifs DNA Breaks Single-Stranded Molecular Biology chemistry.chemical_classification Cell Biology DNA Hydrogen Peroxide DNA-Binding Proteins 030104 developmental biology Enzyme X-ray Repair Cross Complementing Protein 1 chemistry Cytoplasm APEH 030217 neurology & neurosurgery Peptide Hydrolases Protein Binding |
| Zdroj: | DNA repair. 58 |
| ISSN: | 1568-7856 1568-7864 |
| Popis: | Acylpeptide hydrolase (APEH) deacetylates N-alpha-acetylated peptides and selectively degrades oxidised 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. |
| Databáze: | OpenAIRE |
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