TY - JOUR
T1 - DNA-dependent protein kinase
T2 - Epigenetic alterations and the role in genomic stability of cancer
AU - George, Vazhappilly Cijo
AU - Ansari, Shabbir Ahmed
AU - Chelakkot, Vipin Shankar
AU - Chelakkot, Ayshwarya Lakshmi
AU - Chelakkot, Chaithanya
AU - Menon, Varsha
AU - Ramadan, Wafaa
AU - Ethiraj, Kannatt Radhakrishnan
AU - El-Awady, Raafat
AU - Mantso, Theodora
AU - Mitsiogianni, Melina
AU - Panagiotidis, Mihalis I.
AU - Dellaire, Graham
AU - Vasantha Rupasinghe, H. P.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - Cancer
KW - DNA damage
KW - DNA repair
KW - DNA-PK
KW - Epigenetic alternations
KW - Genomic stability
U2 - 10.1016/j.mrrev.2018.06.001
DO - 10.1016/j.mrrev.2018.06.001
M3 - Article
AN - SCOPUS:85050852201
SN - 1383-5742
VL - 780
SP - 92
EP - 105
JO - Mutation Research - Reviews in Mutation Research
JF - Mutation Research - Reviews in Mutation Research
ER -
