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

Vazhappilly Cijo George, Shabbir Ahmed Ansari, Vipin Shankar Chelakkot, Ayshwarya Lakshmi Chelakkot, Chaithanya Chelakkot, Varsha Menon, Wafaa Ramadan, Kannatt Radhakrishnan Ethiraj, Raafat El-Awady, Theodora Mantso, Melina Mitsiogianni, Mihalis I. Panagiotidis, Graham Dellaire, H. P. Vasantha Rupasinghe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)92-105
JournalMutation Research - Reviews in Mutation Research
Volume780
Early online date19 Jun 2018
DOIs
Publication statusPublished - 1 Apr 2019

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