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

Mutation Research. Reviews in Mutation Research
Vazhappilly Cijo GeorgeH P Vasantha Rupasinghe

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.

Citations

Aug 23, 2020·Biomedicines·Shoib Sarwar SiddiquiCijo George Vazhappilly
Dec 9, 2020·Phytotherapy Research : PTR·Cijo George VazhappillyRajan Radhakrishnan
Mar 17, 2020·Mutation Research·Giovanna Damia
Mar 20, 2021·Inflammopharmacology·Sofia RahmanCijo George Vazhappilly
Apr 4, 2021·International Journal of Molecular Sciences·Wasitha P D Wass ThilakarathnaNeale D Ridgway

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