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

Publication date: Available online 19 June 2018Source: Mutation Research/Reviews in Mutation ResearchAuthor(s): Vazhappilly Cijo George, Shabbir 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. Panayiotidis, Graham Dellaire, H.P. Vasantha RupasingheAbstractDNA-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 the immune cell development and protects telomerase during cellular aging. Epigenetic alterations due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn can impair DNA 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 levels as a novel cancer biomarker. In addition, several small molecules and biological agents have been identified recently 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 diff...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research