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

George, Vazhappilly Cijo, Ansari, Shabbir Ahmed, Chelakkot, Vipin Shankar, Chelakkot, Ayshwarya Lakshmi, Chelakkot, Chaithanya, Menon, Varsha, Ramadan, Wafaa, Ethiraj, Kannatt Radhakrishnan, El-Awady, Raafat, Mantso, Theodora, Mitsiogianni, Melina, Panagiotidis, Mihalis, Dellaire, Graham and Vasantha Rupasinghe, H.P. (2019) DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer. Mutation Research/Reviews in Mutation Research, 780. pp. 92-105. ISSN 1383-5742

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Abstract

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.

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