Polyomavirus interaction with the DNA damage response
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Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response (DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATM- and ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.
Keywordspolyomavirus DNA damage response genomic instability mitotic stress
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- Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G, Carattini-Rivera S, DeMayo F, Bradley A, Donehower LA, Elledge SJ. 2000. Chk1 is an essential kinase that is regulated by atr and required for the G(2)/M DNA damage checkpoint. Genes Dev, 14: 1448–1459.CrossRefPubMedCentralPubMedGoogle Scholar
- Pores Fernando AT, Andrabi S, Cizmecioglu O, Zhu C, Livingston DM, Higgins JM, Schaffhausen BS, Roberts TM. 2014. Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene. doi: 10.1038/onc.2014.192.Google Scholar
- Yu G, Greninger AL, Isa P, Phan TG, Martinez MA, de la Luz Sanchez M, Contreras JF, Santos-Preciado JI, Parsonnet J, Miller S, DeRisi JL, Delwart E, Arias CF, Chiu CY. 2012. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One, 7: e49449.CrossRefPubMedCentralPubMedGoogle Scholar
- Zhao X, Madden-Fuentes RJ, Lou BX, Pipas JM, Gerhardt J, Rigell CJ, Fanning E. 2008. Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells. J Virol, 82: 5316–5328.CrossRefPubMedCentralPubMedGoogle Scholar