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

Medicine

Résultat de recherche: Review article › examen par les pairs

13 Citations (Scopus)

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.

Langue d'origine	English
Pages (de-à)	92-105
Nombre de pages	14
Journal	Mutation Research - Reviews in Mutation Research
Volume	780
DOI	https://doi.org/10.1016/j.mrrev.2018.06.001
Statut de publication	Published - avr. 1 2019

Note bibliographique

Funding Information:
Work in HPVR laboratory is funded by Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN 246127). GD is a Senior Scientist at the Beatrice Hunter Cancer Research Institute (BHCRI) and his laboratory’s work on DNA repair is funded by a Discovery Grant from the NSERC (RGPIN 05616).

Publisher Copyright:
© 2018

ASJC Scopus Subject Areas

Genetics
Health, Toxicology and Mutagenesis

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

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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

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

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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.",

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AU - George, Vazhappilly Cijo

AU - Ansari, Shabbir Ahmed

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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.

N1 - Funding Information: Work in HPVR laboratory is funded by Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN 246127). GD is a Senior Scientist at the Beatrice Hunter Cancer Research Institute (BHCRI) and his laboratory’s work on DNA repair is funded by a Discovery Grant from the NSERC (RGPIN 05616). Publisher Copyright: © 2018

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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.

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

Résumé

Note bibliographique

ASJC Scopus Subject Areas

ODD de l’ONU

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