The role of the DNA damage response throughout the papillomavirus life cycle

Viruses

Volumn 7, Issue 5, 2015, Pages 2450-2469

  McKinney, Caleb C ^a   Hussmann, Katherine L ^a   McBride, Alison A ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

DNA damage response; DNA repair; Episome; Homologous recombination; HPV; Keratinocyte; Papillomavirus; Partitioning; Replication; Replication foci

Indexed keywords

CAPSID PROTEIN; VIRUS DNA;

CARCINOGENESIS; CELL DIFFERENTIATION; DNA DAMAGE; DNA INTEGRATION; DNA REPAIR; DNA REPLICATION; DNA SYNTHESIS; EPISOME; GENE AMPLIFICATION; GENE DOSAGE; GENOMIC INSTABILITY; LIFE CYCLE; NONHUMAN; PAPILLOMAVIRIDAE; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; VIRUS PARTICLE; HOST PATHOGEN INTERACTION; METABOLISM; PHYSIOLOGY; VIRUS REPLICATION;

HUMAN PAPILLOMAVIRUS; PAPILLOMAVIRIDAE;

DNA DAMAGE; DNA REPAIR; DNA, VIRAL; HOST-PATHOGEN INTERACTIONS; PAPILLOMAVIRIDAE; VIRUS REPLICATION;

EID: 84930936690     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v7052450     Document Type: Review

References (122)

1. Cubie, H.A. Diseases associated with human papillomavirus infection. Virology 2013,445, 21-34.
2. McLaughlin-Drubin, M.E.; Meyers, J.; Munger, K. Cancer associated human papillomaviruses. Curr. Opin. Virol. 2012,2, 459-466. [CrossRef] [PubMed]
3. Zur Hausen, H. Papillomavirus infections—A major cause of human cancers. Biochim. Biophys. Acta 1996,1288, F55-F78. [PubMed]
4. HPV-Associated Cancers Statistics. Available online: http://www.cdc.gov/cancer/hpv/statistics/ (accessed on 13 March 2015).
5. NIAID The Papillomavirus Episteme. Available online: http://pave.niaid.nih.gov/ (accessed on 13 March 2015).
6. McBride, A.A. Replication and partitioning of papillomavirus genomes. Adv. Virus Res. 2008, 72, 155-205. [PubMed]
7. Mohr, I.J.; Clark, R.; Sun, S.; Androphy, E.J.; MacPherson, P.; Botchan, M.R. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 1990, 250, 1694-1699. [CrossRef] [PubMed]
8. Ustav, M.; Stenlund, A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991, 10, 449-457. [PubMed]
9. Ustav, M.; Ustav, E.; Szymanski, P.; Stenlund, A. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J. 1991,10, 4321-4329. [PubMed]
10. Sanders, C.M.; Stenlund, A. Recruitment and loading of the E1 initiator protein: An ATP-dependent process catalysed by a transcription factor. EMBO J. 1998, 17, 7044-7055.
11. Egawa, N.; Nakahara, T.; Ohno, S.; Narisawa-Saito, M.; Yugawa, T.; Fujita, M.; Yamato, K.; Natori, Y.; Kiyono, T. The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. J. Virol. 2012, 86,3276-3283. [CrossRef] [PubMed]
12. Kim, K.; Lambert, P.F. E1 protein of bovine papillomavirus 1 is not required for the maintenance of viral plasmid DNA replication. Virology 2002, 293, 10-14. [CrossRef] [PubMed]
13. McLaughlin-Drubin, M.E.; Bromberg-White, J.L.; Meyers, C. The role of the human papillomavirus type 18 E7 oncoprotein during the complete viral life cycle. Virology 2005, 338, 61-68. [CrossRef] [PubMed]
14. Flores, E.R.; Allen-Hoffmann, B.L.; Lee, D.; Lambert, P.F. The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J. Virol. 2000, 74, 6622-6631.
15. Chow, L.T.; Duffy, A.A.; Wang, H.K.; Broker, T.R. A highly efficient system to produce infectious human papillomavirus: Elucidation of natural virus-host interactions. Cell Cycle 2009, 8, 1319-1323. [CrossRef] [PubMed]
16. Banerjee, N.S.; Wang, H.K.; Broker, T.R.; Chow, L.T. Human papillomavirus (HPV) E7 induces prolonged G2 following S phase reentry in differentiated human keratinocytes. J. Biol. Chem. 2011, 286, 15473-15482. [CrossRef] [PubMed]
17. Nakahara, T.; Peh, W.L.; Doorbar, J.; Lee, D.; Lambert, P.F. Human papillomavirus type 16 E1AE4 contributes to multiple facets of the papillomavirus life cycle. J. Virol. 2005, 79, 13150-13165.
18. Day, P.M.; Schelhaas, M. Concepts of papillomavirus entry into host cells. Curr. Opin. Virol. 2014, 4, 24-31. [CrossRef] [PubMed]
19. Culp, T.D.; Budgeon, L.R.; Christensen, N.D. Human papillomaviruses bind a basal extracellular matrix component secreted by keratinocytes which is distinct from a membrane-associated receptor. Virology 2006, 347, 147-159. [CrossRef] [PubMed]
20. Day, P.M.; Baker, C.C.; Lowy, D.R.; Schiller, J.T. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc. Natl. Acad. Sci. USA 2004,101, 14252-14257. [CrossRef] [PubMed]
21. Pyeon, D.; Pearce, S.M.; Lank, S.M.; Ahlquist, P.; Lambert, P.F. Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog. 2009, 5, e1000318.
22. Aydin, I.; Weber, S.; Snijder, B.; Samperio Ventayol, P.; Kuhbacher, A.; Becker, M.; Day, P.M.; Schiller, J.T.; Kann, M.; Pelkmans, L. et al. Large scale RNAi reveals the requirement of nuclear envelope breakdown for nuclear import of human papillomaviruses. PLo Pathog. 2014, 10, e1004162. [CrossRef] [PubMed]
23. Evans, M.F.; Aliesky, H.A.; Cooper, K. Optimization of biotinyl-tyramide-based in situ hybridization for sensitive background-free applications on formalin-fixed, paraffin-embedded tissue specimens. BMC Clin. Pathol. 2003, 3, e2. [CrossRef]
24. Peh, W.L.; Middleton, K.; Christensen, N.; Nicholls, P.; Egawa, K.; Sotlar, K.; Brandsma, J.; Percival, A.; Lewis, J.; Liu, W.J. et al. Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J. Virol. 2002, 76, 10401-10416. [CrossRef] [PubMed]
25. Ozbun, M.A. Human papillomavirus type 31b infection of human keratinocytes and the onset of early transcription. J. Virol. 2002, 76, 11291-11300. [CrossRef] [PubMed]
26. Stubenrauch, F.; Hummel, M.; Iftner, T.; Laimins, L.A. The E8E2C protein, a negative regulator of viral transcription and replication, is required for extrachromosomal maintenance of human papillomavirus type 31 in keratinocytes. J. Virol. 2000, 74, 1178-1186. [CrossRef] [PubMed]
27. Botchan, M.; Berg, L.; Reynolds, J.; Lusky, M. The bovine papillomavirus replicon. In Papillomaviruses; John Wiley & Sons: New York, NY, USA, 1986; pp. 53-67.
28. Roberts, J.M.; Weintraub, H. Cis-acting negative control of DNA replication in eukaryotic cells. Cell 1988, 52, 397-404. [CrossRef] [PubMed]
29. Gilbert, D.M.; Cohen, S.N. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell 1987, 50, 59-68. [CrossRef] [PubMed]
30. Ravnan, J.-B.; Gilbert, D.M.; Ten Hagen, K.G.; Cohen, S.N. Random-choice replication of extrachromosomal bovine papillomavirus (BPV) molecules in heterogeneous, clonally derived BPV-infected cell lines. J. Virol. 1992, 66, 6946-6952. [PubMed]
31. Hoffmann, R.; Hirt, B.; Bechtold, V.; Beard, P.; Raj, K. Different modes of human papillomavirus DNA replication during maintenance. J. Virol. 2006, 80, 4431-4439. [CrossRef] [PubMed]
32. Fradet-Turcotte, A.; Moody, C.; Laimins, L.A.; Archambault, J. Nuclear export of human papillomavirus type 31 E1 is regulated by Cdk2 phosphorylation and required for viral genome maintenance. J. Virol. 2010, 84, 11747-11760. [CrossRef] [PubMed]
33. Yu, J.H.; Lin, B.Y.; Deng, W.; Broker, T.R.; Chow, L.T. Mitogen-activated protein kinases activate the nuclear localization sequence of human papillomavirus type 11 E1 DNA helicase to promote efficient nuclear import. J. Virol. 2007, 81, 5066-5078. [CrossRef] [PubMed]
34. Straub, E.; Dreer, M.; Fertey, J.; Iftner, T.; Stubenrauch, F. The viral E8AE2C repressor limits productive replication of human papillomavirus 16. J. Virol. 2014, 88, 937-947.
35. Gunasekharan, V.; Laimins, L.A. Human papillomaviruses modulate microRNA 145 expression to directly control genome amplification. J. Virol. 2013, 87, 6037-6043. [CrossRef] [PubMed]
36. Penrose, K.J.; McBride, A.A. Proteasome-mediated degradation of the papillomavirus E2-TA protein is regulated by phosphorylation and can modulate viral genome copy number. J. Virol. 2000, 74, 6031-6038. [CrossRef] [PubMed]
37. Skiadopoulos, M.H.; McBride, A.A. Bovine papillomavirus type 1 genomes and the E2 transactivator protein are closely associated with mitotic chromatin. J. Virol. 1998, 72, 2079-2088. [PubMed]
38. Ilves, I.; Kivi, S.; Ustav, M. Long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which is mediated by the viral E2 protein and its binding sites. J. Virol. 1999, 73, 4404-4412. [PubMed]
39. Bastien, N.; McBride, A.A. Interaction of the papillomavirus E2 protein with mitotic chromosomes. Virology 2000, 270, 124-134. [CrossRef] [PubMed]
40. McBride, A.A.; Oliveira, J.G.; McPhillips, M.G. Partitioning viral genomes in mitosis: Same idea, different targets. Cell Cycle 2006, 5, 1499-1502. [CrossRef] [PubMed]
41. Oliveira, J.G.; Colf, L.A.; McBride, A.A. Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA 2006, 103, 1047-1052. [CrossRef] [PubMed]
42. Jang, M.K.; Kwon, D.; McBride, A.A. Papillomavirus E2 proteins and the host BRD4 protein associate with transcriptionally active cellular chromatin. J. Virol. 2009, 83, 2592-2600.
43. Jang, M.K.; Shen, K.; McBride, A.A. Papillomavirus genomes associate with BRD4 to replicate at fragile sites in the host genome. PLoS Pathog. 2014,10, e1004117. [CrossRef] [PubMed]
44. Helfer, C.M.; Yan, J.; You, J. The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation. Viruses 2014, 6, 3228-3249.
45. Jang, M.K.; Anderson, D.E.; van Doorslaer, K.; McBride, A.A. A Proteomic approach to discover and compare interacting partners of Papillomavirus E2 proteins from diverse phylogenetic groups. Proteomics 2015. [CrossRef]
46. McBride, A.A. The Papillomavirus E2 proteins. Virology 2013,445, 57-79. [CrossRef] [PubMed]
47. Devaiah, B.N.; Singer, D.S. Two faces of brd4: Mitotic bookmark and transcriptional lynchpin. Transcription 2013, 4, 13-17. [CrossRef] [PubMed]
48. McBride, A.A.; Jang, M.K. Current understanding of the role of the Brd4 protein in the papillomavirus lifecycle. Viruses 2013, 5, 1374-1394. [CrossRef] [PubMed]
49. You, J.; Croyle, J.L.; Nishimura, A.; Ozato, K.; Howley, P.M. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 2004, 117, 349-360. [CrossRef] [PubMed]
50. Baxter, M.K.; McPhillips, M.G.; Ozato, K.; McBride, A.A. The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4. J. Virol. 2005, 79, 4806-4818. [CrossRef] [PubMed]
51. McPhillips, M.G.; Ozato, K.; McBride, A.A. Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin. J. Virol. 2005, 79, 8920-8932.
52. McPhillips, M.G.; Oliveira, J.G.; Spindler, J.E.; Mitra, R.; McBride, A.A. Brd4 is required for e2-mediated transcriptional activation but not genome partitioning of all papillomaviruses. J. Virol. 2006, 80, 9530-9543. [CrossRef] [PubMed]
53. Rahman, S.; Sowa, M.E.; Ottinger, M.; Smith, J.A.; Shi, Y.; Harper, J.W.; Howley, P.M. The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Mol. Cell. Biol. 2011, 31, 2641-2652. [CrossRef] [PubMed]
54. Smith, J.A.; White, E.A.; Sowa, M.E.; Powell, M.L.; Ottinger, M.; Harper, J.W.; Howley, P.M. Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Proc. Natl. Acad. Sci. USA 2010, 107, 3752-3757.
55. Schweiger, M.R.; Ottinger, M.; You, J.; Howley, P.M. Brd4 independent transcriptional repression function of the papillomavirus E2 proteins. J. Virol. 2007, 81, 9612-9622. [CrossRef] [PubMed]
56. Wu, S.Y.; Lee, A.Y.; Hou, S.Y.; Kemper, J.K.; Erdjument-Bromage, H.; Tempst, P.; Chiang, C.M. Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev. 2006, 20, 2383-2396. [CrossRef] [PubMed]
57. Helfer, C.M.; Wang, R.; You, J. Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation. PLoS ONE 2013, 8, e77994.
58. Chang, S.-W.; Liu, W.-C.; Liao, K.-Y.; Tsao, Y.-P.; Hsu, P.-H.; Chen, S.-L. Phosphorylation of HPV-16 E2 at Serine 243 Enables Binding to Brd4 and Mitotic Chromosomes. PLoS ONE 2014, 9,e110882. [CrossRef] [PubMed]
59. Stubenrauch, F.; Colbert, A.M.; Laimins, L.A. Transactivation by the E2 protein of oncogenic human papillomavirus type 31 is not essential for early and late viral functions. J. Virol. 1998, 72, 8115-8123. [PubMed]
60. Senechal, H.; Poirier, G.G.; Coulombe, B.; Laimins, L.A.; Archambault, J. Amino acid substitutions that specifically impair the transcriptional activity of papillomavirus E2 affect binding to the long isoform of Brd4. Virology 2007, 358, 10-17. [CrossRef] [PubMed]
61. Sakakibara, N.; Chen, D.; Jang, M.K.; Kang, D.W.; Luecke, H.F.; Wu, S.Y.; Chiang, C.M.; McBride, A.A. Brd4 Is Displaced from HPV Replication Factories as They Expand and Amplify Viral DNA. PLoS Pathog. 2013, 9, e1003777. [CrossRef] [PubMed]
62. Wang, X.; Helfer, C.M.; Pancholi, N.; Bradner, J.E.; You, J. Recruitment of brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J. Virol. 2013, 87, 3871-3884. [CrossRef] [PubMed]
63. Gauson, E.J.; Donaldson, M.M.; Dornan, E.S.; Wang, X.; Bristol, M.; Bodily, J.M.; Morgan, I.M. Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2 mediated DNA replication. J. Virol. 2015, 89, 4980-4991.
64. Floyd, S.R.; Pacold, M.E.; Huang, Q.; Clarke, S.M.; Lam, F.C.; Cannell, I.G.; Bryson, B.D.; Rameseder, J.; Lee, M.J.; Blake, E.J. et al. The bromodomain protein Brd4 insulates chromatin from DNA damage signalling. Nature 2013, 498, 246-250. [CrossRef] [PubMed]
65. Bedell, M.A.; Hudson, J.B.; Golub, T.R.; Turyk, M.E.; Hosken, M.; Wilbanks, G.D.; Laimins, L.A. Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J. Virol. 1991, 65, 2254-2260. [PubMed]
66. Maglennon, G.A.; Mcintosh, P.; Doorbar, J. Persistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression. Virology 2011, 414, 153-163. [CrossRef] [PubMed]
67. Flores, E.R.; Lambert, P.F. Evidence for a switch in the mode of human papillomavirus type 16 DNA replication during the viral life cycle. J. Virol. 1997, 71, 7167-7179. [PubMed]
68. Burnett, S.; Zabielski, J.; Moreno-Lopez, J.; Pettersson, U. Evidence for multiple vegetative DNA replication origins and alternative replication mechanisms of bovine papillomavirus type 1. J. Mol. Biol. 1989, 206, 239-244. [CrossRef] [PubMed]
69. Moody, C.A.; Laimins, L.A. Human Papillomaviruses Activate the ATM DNA Damage Pathway for Viral Genome Amplification upon Differentiation. PLoS Pathog. 2009, 5, e1000605.
70. Nakamura, J.; Mutlu, E.; Sharma, V.; Collins, L.; Bodnar, W.; Yu, R.; Lai, Y.; Moeller, B.; Lu, K.; Swenberg, J. The endogenous exposome. DNA Repair 2014,19, 3-13. [CrossRef] [PubMed]
71. Jackson, S.P.; Bartek, J. The DNA-damage response in human biology and disease. Nature 2009, 461, 1071-1078. [CrossRef] [PubMed]
72. Stracker, T.H.; Usui, T.; Petrini, J.H. Taking the time to make important decisions: The checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair 2009, 8,1047-1054.
73. Chaurushiya, M.S.; Weitzman, M.D. Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair 2009, 8, 1166-1176. [CrossRef] [PubMed]
74. Luftig, M.A. Viruses and the DNA Damage Response: Activation and Antagonism. Annu. Rev. Virol. 2014, 1, 605-625. [CrossRef]
75. Sowd, G.A.; Li, N.Y.; Fanning, E. ATM and ATR activities maintain replication fork integrity during SV40 chromatin replication. PLoS Pathog. 2013, 9, e1003283. [CrossRef] [PubMed]
76. Sowd, G.A.; Mody, D.; Eggold, J.; Cortez, D.; Friedman, K.L.; Fanning, E. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products. PLoS Pathog. 2014,10, e1004536. [CrossRef] [PubMed]
77. Sakakibara, N.; Mitra, R.; McBride, A.A. The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J. Virol. 2011, 85, 8981-8995. [CrossRef] [PubMed]
78. Fradet-Turcotte, A.; Bergeron-Labrecque, F.; Moody, C.A.; Lehoux, M.; Laimins, L.A.; Archambault, J. Nuclear accumulation of the papillomavirus E1 helicase blocks S-phase progression and triggers an ATM-dependent DNA damage response. J. Virol. 2011, 85, 8996-9012. [CrossRef] [PubMed]
79. Gillespie, K.A.; Mehta, K.P.; Laimins, L.A.; Moody, C.A. Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers. J. Virol. 2012, 86, 9520-9526. [CrossRef] [PubMed]
80. Reinson, T.; Toots, M.; Kadaja, M.; Pipitch, R.; Allik, M.; Ustav, E.; Ustav, M. Engagement of the ATR-Dependent DNA Damage Response at the Human Papillomavirus 18 Replication Centers during the Initial Amplification. J. Virol. 2013, 87, 951-964. [CrossRef] [PubMed]
81. Kanginakudru, S.; DeSmet, M.; Thomas, Y.; Morgan, I.M.; Androphy, E.J. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication. Virology 2015, 478, 135-142. [CrossRef] [PubMed]
82. Sakakibara, N.; Chen, D.; McBride, A.A. Papillomaviruses use recombination-dependent replication to vegetatively amplify their genomes in differentiated cells. PLoS Pathog. 2013, 9, e1003321. [CrossRef] [PubMed]
83. Swindle, C.S.; Zou, N.; van Tine, B.A.; Shaw, G.M.; Engler, J.A.; Chow, L.T. Human papillomavirus DNA replication compartments in a transient DNA replication system. J. Virol. 1999, 73, 1001-1009. [PubMed]
84. Stepp, W.H.; Meyers, J.M.; McBride, A.A. Sp100 provides intrinsic immunity against human papillomavirus infection. MBio 2013, 4, e00845-13. [CrossRef] [PubMed]
85. Everett, R.D. Interactions between DNA viruses, ND10 and the DNA damage response. Cell. Microbiol. 2006, 8, 365-374. [CrossRef] [PubMed]
86. King, L.E.; Fisk, J.C.; Dornan, E.S.; Donaldson, M.M.; Melendy, T.; Morgan, I.M. Human papillomavirus E1 and E2 mediated DNA replication is not arrested by DNA damage signalling. Virology 2010, 406, 95-102. [CrossRef] [PubMed]
87. Lorenz, L.D.; Rivera Cardona, J.; Lambert, P.F. Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6. PLoS Pathog. 2013, 9, e1003717.
88. Lace, M.J.; Turek, L.P.; Anson, J.R.; Haugen, T.H. Analyzing the Human Papillomavirus (HPV) Life Cycle in Primary Keratinocytes with a Quantitative Colony-Forming Assay. Curr. Protoc. Microbiol. 2014, 33, 14b.2.1-14b.2.13. [PubMed]
89. Leight, E.R.; Sugden, B. Establishment of an oriP replicon is dependent upon an infrequent, epigenetic event. Mol. Cell. Biol. 2001, 21, 4149-4161. [CrossRef] [PubMed]
90. Edwards, T.G.; Helmus, M.J.; Koeller, K.; Bashkin, J.K.; Fisher, C. Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways. J. Virol. 2013, 87, 3979-3989. [CrossRef] [PubMed]
91. Edwards, T.G.; Vidmar, T.J.; Koeller, K.; Bashkin, J.K.; Fisher, C. DNA damage repair genes controlling human papillomavirus (HPV) episome levels under conditions of stability and extreme instability. PLoS ONE 2013, 8, e75406. [CrossRef] [PubMed]
92. Pickering, M.T.; Debatis M.; Castillo, J.; Lagadinos, A.; Wang, S.; Lu, S.; Kowalik, T.F. An E2F1-mediated DNA damage response contributes to the replication of human cytomegalovirus. PLoS Pathog. 2011, 7, e1001342. [CrossRef] [PubMed]
93. Rogoff, H.A.; Pickering, M.T.; Frame, F.M.; Debatis, M.E.; Sanchez, Y.; Jones, S.; Kowalik, T.F. Apoptosis associated with deregulated E2F activity is dependent on E2F1 and Atm/Nbs1/Chk2. Mol. Cell. Biol. 2004, 24, 2968-2977. [CrossRef] [PubMed]
94. Bester, A.C.; Roniger, M.; Oren, Y.S.; Im, M.M.; Sarni, D.; Chaoat, M.; Bensimon, A.; Zamir, G.; Shewach, D.S.; Kerem, B. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011,145, 435-446. [CrossRef] [PubMed]
95. Spardy, N.; Covella, K.; Cha, E.; Hoskins, E.E.; Wells, S.I.; Duensing, A.; Duensing, S. Human papillomavirus 16 E7 oncoprotein attenuates DNA damage checkpoint control by increasing the proteolytic turnover of claspin. Cancer Res. 2009, 69,7022-7029. [CrossRef] [PubMed]
96. Thomas, J.T.; Hubert, W.G.; Ruesch, M.N.; Laimins, L.A. Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. Proc. Natl. Acad. Sci. USA 1999, 96, 8449-8454.
97. Park, R.B.; Androphy, E.J. Genetic analysis of high-risk e6 in episomal maintenance of human papillomavirus genomes in primary human keratinocytes. J. Virol. 2002, 76, 11359-11364.
98. Brimer, N.; Vande Pol, S.B. Papillomavirus E6 PDZ interactions can be replaced by repression of p53 to promote episomal human papillomavirus genome maintenance. J. Virol. 2014, 88, 3027-3030. [CrossRef] [PubMed]
99. Klumpp, D.J.; Laimins, L.A. Differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein E1. Virology 1999, 257, 239-246.
100. Anacker, D.C.; Gautam, D.; Gillespie, K.A.; Chappell, W.H.; Moody, C.A. Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1. J. Virol. 2014, 88, 8528-8544.
101. Hong, S.; Laimins, L.A. The JAK-STAT Transcriptional Regulator, STAT-5, Activates the ATM DNA Damage Pathway to Induce HPV 31 Genome Amplification upon Epithelial Differentiation. PLoS Pathog. 2013, 9, e1003295. [CrossRef] [PubMed]
102. Kho, E.Y.; Wang, H.K.; Banerjee, N.S.; Broker, T.R.; Chow, L.T. HPV-18 E6 mutants reveal p53 modulation of viral DNA amplification in organotypic cultures. Proc. Natl. Acad. Sci. USA 2013, 110, 7542-7549. [CrossRef] [PubMed]
103. Lepik, D.; Ilves, I.; Kristjuhan, A.; Maimets, T.; Ustav, M. p53 protein is a suppressor of papillomavirus DNA amplificational replication. J. Virol. 1998, 72, 6822-6831.
104. Ilves, I.; Kadaja, M.; Ustav, M. Two separate replication modes of the bovine papillomavirus BPV1 origin of replication that have different sensitivity to p53. Virus Res. 2003, 96, 75-84.
105. Akgul, B.; Karle, P.; Adam, M.; Fuchs, P.G.; Pfister, H.J. Dual role of tumor suppressor p53 in regulation of DNA replication and oncogene E6-promoter activity of epidermodysplasia verruciformis-associated human papillomavirus type 8. Virology 2003, 308, 279-290.
106. Brown, C.; Kowalczyk, A.M.; Taylor, E.R.; Morgan, I.M.; Gaston, K. P53 represses human papillomavirus type 16 DNA replication via the viral E2 protein. Virol. J. 2008, 5, e5. [CrossRef]
107. Dasgupta, S.; Zabielski, J.; Simonsson, M.; Burnett, S. Rolling-circle replication of a high-copy BPV-1 plasmid. J. Mol. Biol. 1992, 228, 1-6. [CrossRef] [PubMed]
108. Auborn, K.J.; Little, R.D.; Platt, T.H.; Vaccariello, M.A.; Schildkraut, C.L. Replicative intermediates of human papillomavirus type 11 in laryngeal papillomas: Site of replication initiation and direction of replication. Proc. Natl. Acad. Sci. USA 1994, 91, 7340-7344.
109. Lydeard, J.R.; Lipkin-Moore, Z.; Sheu, Y.J.; Stillman, B.; Burgers, P.M.; Haber, J.E. Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev. 2010, 24, 1133-1144. [CrossRef] [PubMed]
110. Wallace, N.A.; Robinson, K.; Howie, H.L.; Galloway, D.A. HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage. PLoS Pathog. 2012, 8, e1002807. [CrossRef] [PubMed]
111. Wallace, N.A.; Galloway, D.A. Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin. Cancer Biol. 2014, 26, 30-42.
112. Wallace, N.A.; Robinson, K.; Galloway, D.A. Beta human papillomavirus E6 expression inhibits stabilization of p53 and increases tolerance of genomic instability. J. Virol. 2014, 88, 6112-6127.
113. Wallace, N.A.; Robinson, K.; Howie, H.L.; Galloway, D.A. beta-HPV 5 and 8 E6 Disrupt Homology Dependent Double Strand Break Repair by Attenuating BRCA1 and BRCA2 Expression and Foci Formation. PLoS Pathog. 2015,11, e1004687. [CrossRef] [PubMed]
114. Jackson, S.; Storey, A. E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage. Oncogene 2000, 19, 592-598. [CrossRef] [PubMed]
115. Giampieri, S.; Storey, A. Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18. Br. J. Cancer 2004, 90, 2203-2209. [PubMed]
116. Holloway, A.; Simmonds, M.; Azad, A.; Fox, J.L.; Storey, A. Resistance to UV-induced apoptosis by beta-HPV5 E6 involves targeting of activated BAK for proteolysis by recruitment of the HERC1 ubiquitin ligase. Int. J. Cancer J. Int. Cancer 2015,136, 2831-2843. [CrossRef]
117. Durst, M.; Gissmann, L.; Ikenberg, H.; zur Hausen, H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc. Natl. Acad. Sci. USA 1983, 80, 3812-3815. [CrossRef] [PubMed]
118. Thorland, E.C.; Myers, S.L.; Gostout, B.S.; Smith, D.I. Common fragile sites are preferential targets for HPV16 integrations in cervical tumors. Oncogene 2003, 22, 1225-1237.
119. Smith, P.P.; Friedman, C.L.; Bryant, E.M.; McDougall, J.K. Viral integration and fragile sites in human papillomavirus-immortalized human keratinocyte cell lines. Genes Chromosomes Cancer 1992, 5, 150-157. [CrossRef] [PubMed]
120. Akagi, K.; Li, J.; Broutian, T.R.; Padilla-Nash, H.; Xiao, W.; Jiang, B.; Rocco, J.W.; Teknos, T.N.; Kumar, B.; Wangsa, D.; et al. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2013. [CrossRef]
121. Kadaja, M.; Sumerina, A.; Verst, T.; Ojarand, M.; Ustav, E.; Ustav, M. Genomic instability of the host cell induced by the human papillomavirus replication machinery. EMBO J. 2007, 26, 2180-2191. [CrossRef] [PubMed]
122. Kadaja, M.; Isok-Paas, H.; Laos, T.; Ustav, E.; Ustav, M. Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses. PLoS Pathog. 2009, 5, e1000397.