Modulation of the DNA damage response during the life cycle of human papillomaviruses.
Human papillomavirus (HPV) is the most common sexually transmitted viral infection. Infection with certain types of HPV pose a major public health risk as these types are associated with multiple human cancers, including cervical cancer, other anogenital malignancies and an increasing number of head and neck cancers. The HPV life cycle is closely tied to host cell differentiation with late viral events such as structural gene expression and viral genome amplification taking place in the upper layers of the stratified epithelium. The DNA damage response (DDR) is an elaborate signaling network of proteins that regulate the fidelity of replication by detecting, signaling and repairing DNA lesions. ATM and ATR are two kinases that are major regulators of DNA damage detection and repair. A multitude of studies indicate that activation of the ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3-related) pathways are critical for HPV to productively replicate. This review outlines how HPV interfaces with the ATM- and ATR-dependent DNA damage responses throughout the viral life cycle to create an environment supportive of viral replication and how activation of these pathways could impact genomic stability.
Lineberger Comprehensive Cancer Center and the Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC, USA.
Daniel C
DC
Anacker
Lineberger Comprehensive Cancer Center and the Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC, USA. Electronic address: camoody@med.unc.edu.
Cary A
CA
Moody
D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015398:Signal Transduction; D014779:Virus Replication
D018797:Cell Cycle Proteins; D009856:Oncogene Proteins, Viral; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
DNA damage; Life cycle; Papillomavirus; Viral replication