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

doi:10.1016/j.mrrev.2018.06.001

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

University of Sharjah

Dalhousie University
The University of Texas Health Science Center at Tyler
Memorial University of Newfoundland
Duke-NUS Medical School
Pohang University of Science and Technology
Vellore Institute of Technology
Cairo University
Northumbria University

Research output: Contribution to journal › Review article › peer-review

14 Scopus citations

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 language	English
Pages (from-to)	92-105
Number of pages	14
Journal	Mutation Research - Reviews in Mutation Research
Volume	780
DOIs	https://doi.org/10.1016/j.mrrev.2018.06.001
State	Published - 1 Apr 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cancer
DNA damage
DNA repair
DNA-PK
Epigenetic alternations
Genomic stability

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10.1016/j.mrrev.2018.06.001

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George, V. C., Ansari, S. A., Chelakkot, V. S., Chelakkot, A. L., Chelakkot, C., Menon, V., Ramadan, W., Ethiraj, K. R., El-Awady, R., Mantso, T., Mitsiogianni, M., Panagiotidis, M. I., Dellaire, G., & Vasantha Rupasinghe, H. P. (2019). DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer. Mutation Research - Reviews in Mutation Research, 780, 92-105. https://doi.org/10.1016/j.mrrev.2018.06.001

@article{b2c940a2a6fd4498b5681b886aa0144e,

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

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.",

keywords = "Cancer, DNA damage, DNA repair, DNA-PK, Epigenetic alternations, Genomic stability",

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

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year = "2019",

month = apr,

day = "1",

doi = "10.1016/j.mrrev.2018.06.001",

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George, VC, Ansari, SA, Chelakkot, VS, Chelakkot, AL, Chelakkot, C, Menon, V , Ramadan, W, Ethiraj, KR, El-Awady, R, Mantso, T, Mitsiogianni, M, Panagiotidis, MI, Dellaire, G & Vasantha Rupasinghe, HP 2019, 'DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer', Mutation Research - Reviews in Mutation Research, vol. 780, pp. 92-105. https://doi.org/10.1016/j.mrrev.2018.06.001

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

UR - https://www.scopus.com/pages/publications/85050852201

U2 - 10.1016/j.mrrev.2018.06.001

DO - 10.1016/j.mrrev.2018.06.001

M3 - Review article

C2 - 31395353

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 -

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

Abstract

UN SDGs

Keywords

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