Acylpeptide hydrolase is a component of the cellular response to DNA damage |
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| Institution: | 1. Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824, USA;2. Department of Biology and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA;3. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA;1. Division of Hematology, Department of Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Blvd., Bronx, NY 10461, United States;2. California Institute of Technology, Beckman Institute, Proteome Exploration Laboratory, 1200 E California Blvd, MC139-74, Pasadena, CA 91125, United States;3. Division of Genetics and Metabolism, Center for Hospital-based Specialties, Children''s National Medical Center, 111 Michigan Ave. N.W., Washington, DC 20010-2970, United States |
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| Abstract: | 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. |
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| Keywords: | DNA repair XRCC1 DNA strand breaks |
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