DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer.

Autor: George VC; Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates., Ansari SA; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States., Chelakkot VS; Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada., Chelakkot AL; Duke-NUS Medical School, Singapore., Chelakkot C; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea., Menon V; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates., Ramadan W; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Ethiraj KR; School of Advanced Sciences, VIT University, Vellore, India., El-Awady R; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; Cancer Biology Department, National Cancer Institute and College of Medicine, Cairo University, Cairo, Egypt., Mantso T; Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom., Mitsiogianni M; Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom., Panagiotidis MI; Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom., Dellaire G; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada., Vasantha Rupasinghe HP; Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. Electronic address: vrupasinghe@dal.ca.
Jazyk: angličtina
Zdroj: Mutation research. Reviews in mutation research [Mutat Res Rev Mutat Res] 2019 Apr - Jun; Vol. 780, pp. 92-105. Date of Electronic Publication: 2018 Jun 19.
DOI: 10.1016/j.mrrev.2018.06.001
Abstrakt: DNA-dependent protein kinase (DNA-PK), a member of phosphatidylinositol-kinase family, is a key protein in mammalian DNA double-strand break (DSB) repair that helps to maintain genomic integrity. DNA-PK also plays a central role in immune cell development and protects telomerase during cellular aging. Epigenetic deregulation due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn could impair DNA repair and contribute to genomic instability. Recent studies implicate a role for epigenetics in the regulation of DNA-PK expression in normal and cancer cells, which may impact cancer progression and metastasis as well as provide opportunities for treatment and use of DNA-PK as a novel cancer biomarker. In addition, several small molecules and biological agents have been recently identified that can inhibit DNA-PK function or expression, and thus hold promise for cancer treatments. This review discusses the impact of epigenetic alterations and the expression of DNA-PK in relation to the DNA repair mechanisms with a focus on its differential levels in normal and cancer cells.
(Copyright © 2018. Published by Elsevier B.V.)
Databáze: MEDLINE
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