Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses
- PMID: 24412279
- PMCID: PMC4050178
- DOI: 10.1016/j.semcancer.2013.12.003
Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses
Abstract
In general, the interplay among viruses and DNA damage repair (DDR) pathways can be divided based on whether the interaction promotes or inhibits the viral lifecycle. The propagation of human papillomaviruses is both promoted and inhibited by DDR proteins. As a result, HPV proteins both activate repair pathways, such as the ATM and ATR pathways, and inhibit other pathways, most notably the p53 signaling pathway. Indeed, the role of HPV proteins, with regard to the DDR pathways, can be divided into two broad categories. The first set of viral proteins, HPV E1 and E2 activate a DNA damage response and recruit repair proteins to viral replication centers, where these proteins are likely usurped to replicate the viral genome. Because the activation of the DDR response typically elicits a cell cycle arrest that would impeded the viral lifecycle, the second set of HPV proteins, HPV E6 and E7, prevents the DDR response from pausing cell cycle progression or inducing apoptosis. This review provides a detailed account of the interactions among HPV proteins and DDR proteins that facilitate HPV propagation.
Keywords: DNA damage repair; HPV; HPV replication.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Conflict of interest statement
The authors declare that they have no conflicts of interest.
Figures


Similar articles
-
Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling.Viruses. 2017 Sep 21;9(10):268. doi: 10.3390/v9100268. Viruses. 2017. PMID: 28934154 Free PMC article. Review.
-
Spatial and Functional Organization of Human Papillomavirus Replication Foci in the Productive Stage of Infection.mBio. 2021 Dec 21;12(6):e0268421. doi: 10.1128/mBio.02684-21. Epub 2021 Nov 9. mBio. 2021. PMID: 34749533 Free PMC article.
-
Regulation of the Human Papillomavirus Life Cycle by DNA Damage Repair Pathways and Epigenetic Factors.Viruses. 2020 Jul 10;12(7):744. doi: 10.3390/v12070744. Viruses. 2020. PMID: 32664381 Free PMC article. Review.
-
Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers.J Virol. 2012 Sep;86(17):9520-6. doi: 10.1128/JVI.00247-12. Epub 2012 Jun 27. J Virol. 2012. PMID: 22740399 Free PMC article.
-
Human Papillomaviruses Preferentially Recruit DNA Repair Factors to Viral Genomes for Rapid Repair and Amplification.mBio. 2018 Feb 13;9(1):e00064-18. doi: 10.1128/mBio.00064-18. mBio. 2018. PMID: 29440569 Free PMC article.
Cited by
-
Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.Gynecol Oncol. 2015 Mar;136(3):554-61. doi: 10.1016/j.ygyno.2014.12.035. Epub 2015 Jan 2. Gynecol Oncol. 2015. PMID: 25560806 Free PMC article.
-
The Role of Ataxia Telangiectasia Mutant and Rad3-Related DNA Damage Response in Pathogenesis of Human Papillomavirus.Pathogens. 2020 Jun 23;9(6):506. doi: 10.3390/pathogens9060506. Pathogens. 2020. PMID: 32585979 Free PMC article. Review.
-
The Role of the DNA Damage Response throughout the Papillomavirus Life Cycle.Viruses. 2015 May 21;7(5):2450-69. doi: 10.3390/v7052450. Viruses. 2015. PMID: 26008695 Free PMC article. Review.
-
HPV disease transmission protection and control.Microb Cell. 2016 Sep 5;3(9):476-490. doi: 10.15698/mic2016.09.530. Microb Cell. 2016. PMID: 28357382 Free PMC article. Review.
-
How Chaotic Is Genome Chaos?Cancers (Basel). 2021 Mar 17;13(6):1358. doi: 10.3390/cancers13061358. Cancers (Basel). 2021. PMID: 33802828 Free PMC article. Review.
References
-
- Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362:709–715. - PubMed
-
- Boyer J, Rohleder K, Ketner G. Adenovirus E4 34k and E4 11k inhibit double strand break repair and are physically associated with the cellular DNA-dependent protein kinase. Virology. 1999;263:307–312. - PubMed
-
- Stracker TH, Carson CT, Weitzman MD. Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature. 2002;418:348–352. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous