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The DNA damage response in viral-induced cellular transformation

The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechani...

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Autores principales: Nikitin, P A, Luftig, M A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273341/
https://www.ncbi.nlm.nih.gov/pubmed/22240795
http://dx.doi.org/10.1038/bjc.2011.612
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author Nikitin, P A
Luftig, M A
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Luftig, M A
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description The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation.
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spelling pubmed-32733412013-01-31 The DNA damage response in viral-induced cellular transformation Nikitin, P A Luftig, M A Br J Cancer Minireview The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation. Nature Publishing Group 2012-01-31 2012-01-12 /pmc/articles/PMC3273341/ /pubmed/22240795 http://dx.doi.org/10.1038/bjc.2011.612 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Minireview
Nikitin, P A
Luftig, M A
The DNA damage response in viral-induced cellular transformation
title The DNA damage response in viral-induced cellular transformation
title_full The DNA damage response in viral-induced cellular transformation
title_fullStr The DNA damage response in viral-induced cellular transformation
title_full_unstemmed The DNA damage response in viral-induced cellular transformation
title_short The DNA damage response in viral-induced cellular transformation
title_sort dna damage response in viral-induced cellular transformation
topic Minireview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273341/
https://www.ncbi.nlm.nih.gov/pubmed/22240795
http://dx.doi.org/10.1038/bjc.2011.612
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