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


Journal

Mutation research. Reviews in mutation research
ISSN: 1388-2139
Titre abrégé: Mutat Res Rev Mutat Res
Pays: Netherlands
ID NLM: 101632211

Informations de publication

Date de publication:
Historique:
received: 22 02 2018
accepted: 13 06 2018
entrez: 10 8 2019
pubmed: 10 8 2019
medline: 3 3 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31395353
pii: S1383-5742(18)30013-9
doi: 10.1016/j.mrrev.2018.06.001
pii:
doi:

Substances chimiques

DNA-Activated Protein Kinase EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

92-105

Informations de copyright

Copyright © 2018. Published by Elsevier B.V.

Auteurs

Vazhappilly Cijo George (VC)

Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.

Shabbir Ahmed Ansari (SA)

Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.

Vipin Shankar Chelakkot (VS)

Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

Ayshwarya Lakshmi Chelakkot (AL)

Duke-NUS Medical School, Singapore.

Chaithanya Chelakkot (C)

Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.

Varsha Menon (V)

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.

Wafaa Ramadan (W)

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Kannatt Radhakrishnan Ethiraj (KR)

School of Advanced Sciences, VIT University, Vellore, India.

Raafat El-Awady (R)

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; Cancer Biology Department, National Cancer Institute and College of Medicine, Cairo University, Cairo, Egypt.

Theodora Mantso (T)

Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.

Melina Mitsiogianni (M)

Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.

Mihalis I Panagiotidis (MI)

Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.

Graham Dellaire (G)

Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.

H P Vasantha Rupasinghe (HP)

Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. Electronic address: vrupasinghe@dal.ca.

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Classifications MeSH