Papillomavirus E1 Protein Binds to and Stimulates
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病菌学杂志 2006年第3期
University at Buffalo, Department of Microbiology and Immunology and Witebsky Center for Microbial Pathogenesis, 210 Biomedical Research Building, School of Medicine and Biomedical Sciences, Buffalo, New York 14214
ABSTRACT
The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular DNA replication factors, such as replication protein A or polymerase -primase, to replicate PV genomes. Here, E1 is shown to bind to human topoisomerase I and stimulate its relaxation activity up to sevenfold. The interaction between E1 and topoisomerase I was mapped to the E1 DNA binding domain and C terminus. These findings imply a mechanism for the recruitment of topoisomerase I to PV DNA replication forks and for stimulating topoisomerase I to allow for efficient relaxation of the torsional stress induced by replication fork progression.
TEXT
Papillomaviruses (PVs) are small, nonenveloped, circular DNA viruses (6, 10, 14). The PV E1 protein binds to the PV origin (along with the PV E2 protein), assembles into a hexameric ATP-dependant DNA helicase, and recruits cellular replication factors that work in concert with E1 to replicate the viral genomes (17, 20, 21, 24). E1 has been shown to bind and recruit the cellular factors replication protein A (RPA) and DNA polymerase -primase (2, 6, 12, 13, 15).
One of the essential cellular factors required for PV DNA replication is human topoisomerase I (topoI) (11, 27). topoI is an ATP independent protein that modifies the topology of supercoiled DNA, acting as a swivel to decrease torsional stress on DNA (3, 4, 22). Topoisomerases are important during many cellular processes, such as DNA replication, segregation of daughter chromosomes, modulating nucleosomal structure, transcription, DNA supercoiling, recombination, DNA repair, and genomic stability (8, 18, 25, 26). During the initial stages of DNA replication, the strands of the DNA helix must be separated and the resulting overtwisting of the adjacent DNA must be relieved. Helicases and topoisomerases have been proposed to act together as a "swivelase," instrumental to overcoming these topological obstacles (8). The protein complex that is produced when a helicase and a topoisomerase interact, such as E1-topoI, may be a key step in initiation and play a major role in elongation of DNA replication (8, 19).
The PV E1 protein and human topoI interact. To ascertain whether the PV E1 protein interacts with human topoI, enzyme-linked immunosorbent assay (ELISA)-based protein interaction assays were performed as described previously (12). Purified topoI was immobilized in ELISA plate wells, GST-E1 (human papillomavirus type 11 [HPV-11] or bovine papillomavirus [BPV-1]) was added, and binding was clearly detected (Fig. 1a). Glutathione S-transferase (GST)-YY1, GST, and bovine serum albumin (BSA) did not interact with topoI (Fig. 1a and data not shown). Previous results have demonstrated that GST-E1 also does not interact with other proteins such as SSB or the RPA 32/14 subcomplex (12). topoI was also shown to bind to immobilized GST-E1 and not GST or BSA (Fig. 1b). GST coprecipitations also demonstrated an interaction between E1 and topoI. Glutathione beads were incubated with GST-E1 and 293 cell extract (or purified topoI). Following incubation, the beads were washed in buffer containing 500 mM NaCl and subjected to Western blot analysis (Fig. 1c). These results demonstrate that E1 binds to topoI not only as purified proteins but also within the context of crude cell extracts.
E1 stimulates topoI activity. To determine whether the E1-topoI interaction modulates topoI activity, topoI relaxation assays were performed in the presence and absence of GST-E1 essentially as described previously (22). Increasing amounts of GST-E1 led to a substantial increase in topoI activity (greater than sixfold) (Fig. 2a and b). GST-E1 in the absence of topoI had no intrinsic relaxation activity (Fig. 2a, lane 7). GST, GST-YY1, and additional BSA did not stimulate the relaxation activity of topoI (Fig. 2b). PV origin (BPV-1 and HPV-11) and nonorigin DNA templates were both tested for E1 stimulation of relaxation. All templates showed similar degrees of stimulation by E1, indicating that the presence of a PV origin had no effect on the stimulation of topoI (Fig. 2c and data not shown).
Mapping the E1-topoI interaction. To determine the domains within E1 that interact with topoI, GST-E1 truncation mutants were used in ELISAs. HPV-11 GST-E1 containing amino acids (aa) 1 through 403 of E1 showed a positive interaction with topoI (Fig. 3a, open squares), albeit to a slightly lower level than full-length E1. Conversely, the smaller GST-E1 truncation mutant (aa 1 through 165) showed no significant binding to topoI (Fig. 3a, x). The region between E1 amino acids 165 and 403 encompasses the HPV-11 E1 DNA binding domain (DBD), which consists of amino acids 181 through 353 (1, 23). The homologous BPV-1 E1 DBD (consisting of corresponding amino acids 142 through 308) (5, 9, 16) was also purified and tested for topoI binding using ELISA. The BPV-1 E1 DBD demonstrated a positive interaction, suggesting that the E1 DBD contains a bona fide topoI binding site (Fig. 3a, open triangles, binding site A).
Three amino-terminal HPV-11 GST-E1 truncation mutants were also purified and tested for topoI binding using ELISAs. HPV-11 GST-E1 truncation mutants of aa 310 through 649, aa 346 through 649, and aa 589 through 649, which contain all or part of the core helicase domain (1, 7, 13), all demonstrated a similar positive interaction with topoI (Fig. 3b). From these data, we conclude that the minimal topoI binding site within the C terminus of E1 is within aa 589 through 649 (binding site B). The schematic map of E1 depicts the two domains (sites A and B) within E1 that bind to topoI (Fig. 3c).
E1 truncation mutants and topoI relaxation activity. Plasmid relaxation assays were implemented to assess which of the binding domains affect topoI activity. For each E1 truncation, control reactions were performed in parallel to establish basal topoI relaxation activity and full-length E1's ability to stimulate topoI. As demonstrated above, full-length E1 stimulated topoI approximately sixfold while GST and BSA alone had little effect (Fig. 4a, lanes 8, 2, and 4, respectively). The fragment from aa 1 through 165 E1, which does not bind to topoI, did not stimulate topoI relaxation activity (Fig. 4a, lane 7). The E1 fragment from aa 1 through 403, which binds to topoI, stimulated relaxation activity approximately 3.5-fold (Fig. 4a, lane 10; see also Fig. 4b for quantitation). However, the BPV-1 E1 DBD (Fig. 3c, binding site A) showed no appreciable stimulation of topoI (Fig. 4a, lane 6). This result appears to contrast with the result for the fragment from aa 1 through 403, for which the E1 DBD appeared to be the relevant binding domain. It is possible that aa 1 through 403 may contain amino acid residues outside the E1 DBD that play an ancillary role in the E1-topoI interaction.
Binding site B (the C-terminal E1 fragment, aa 589 through 649) stimulated topoI relaxation activity about half as efficiently as full-length E1 (3.5-fold) (Fig. 4a, lane 5). The two other C-terminal fragments tested (aa 310 through 649 and aa 346 through 649) also stimulated topoI relaxation activity to a similar degree as binding site B (data not shown). All truncations were assayed at the same molar equivalent of full-length E1 (Fig. 4b). The E1 aa 1 through 403 and C-terminal fragments could increase the stimulation of topoI up to 4.5-fold at concentrations at a greater than 1:1 molar ratio (data not shown).
Discussion. In this study, we demonstrated that human topoI binds two distinct regions within the PV E1 protein, the DBD and the C terminus. Using ELISAs and topoI relaxation assays, we demonstrated that of the two minimal regions within E1 that bind topoI, the C-terminal region stimulates topoI relaxation activity as well as the fragment from aa 1 through 403 (which contains binding site A, the DBD), although to a lesser degree. The BPV-1 E1 DBD itself did not stimulate topoI relaxation, indicating that an additional region located within the aa 1 through 403 fragment may be necessary for stimulation. It is unclear at this time how E1 stimulates topoI. Two possibilities are that E1 stimulates the catalytic activity of topoI or that E1 may affect the turnover rate of topoI on DNA. In either case, it is reasonable to suggest that the E1-topoI interaction may be an important aspect of PV DNA replication.
Now that a potential role for the novel E1-topoI interaction has been determined, it will be interesting to ascertain whether topoI stimulates the recruitment of E1 to PV origin sequences and whether E2 plays any role in this interaction.
ACKNOWLEDGMENTS
We thank Jen-Sing Liu, Shu-Ru Kuo, and all members of the Witebsky Center for Microbial Pathogenesis at the University at Buffalo for invaluable scientific discussion. We also thank Te Chung Lee for GST-YY1 protein and J. J. Champoux for the human topoI baculovirus vector. We also thank Dennis McCance for supplying E1 vectors and Meghan Barnhart for her work on this project. Thank you to Yan Hu for purified human topoI preparations. Also, thanks to Philippe Clertant for his help on this project. Thanks to Ed Niles and Mark Sutton for critical reading of the manuscript.
This work was supported by NIH grant R29 GM56406 to T.M. R.V.C. was also supported in part by NIH training grant AI07614.
REFERENCES
Amin, A. A., S. Titolo, A. Pelletier, D. Fink, M. G. Cordingley, and J. Archambault. 2000. Identification of domains of the HPV11 E1 protein required for DNA replication in vitro. Virology 272:137-150.
Bonne-Andrea, C., S. Santucci, P. Clertant, and F. Tillier. 1995. Bovine papillomavirus E1 protein binds specifically DNA polymerase alpha but not replication protein A. J. Virol. 69:2341-2350.
Champoux, J. J. 2001. DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70:369-413.
Champoux, J. J. 2002. A first view of the structure of a type IA topoisomerase with bound DNA. Trends Pharmacol. Sci. 23:199-201.
Chen, G., and A. Stenlund. 1998. Characterization of the DNA-binding domain of the bovine papillomavirus replication initiator E1. J. Virol. 72:2567-2576.
Conger, K. L., J. S. Liu, S. R. Kuo, L. T. Chow, and T. S. Wang. 1999. Human papillomavirus DNA replication. Interactions between the viral E1 protein and two subunits of human DNA polymerase alpha/primase. J. Biol. Chem. 274:2696-2705.
Dixon, E. P., G. L. Pahel, W. J. Rocque, J. A. Barnes, D. C. Lobe, M. H. Hanlon, K. A. Alexander, S. F. Chao, K. Lindley, and W. C. Phelps. 2000. The E1 helicase of human papillomavirus type 11 binds to the origin of replication with low sequence specificity. Virology 270:345-357.
Duguet, M. 1997. When helicase and topoisomerase meet! J. Cell Sci. 110:1345-1350.
Gillitzer, E., G. Chen, and A. Stenlund. 2000. Separate domains in E1 and E2 proteins serve architectural and productive roles for cooperative DNA binding. EMBO J. 19:3069-3079.
Han, Y., Y. M. Loo, K. T. Militello, and T. Melendy. 1999. Interactions of the papovavirus DNA replication initiator proteins, bovine papillomavirus type 1 E1 and simian virus 40 large T antigen, with human replication protein A. J. Virol. 73:4899-4907.
Kuo, S. R., J. S. Liu, T. R. Broker, and L. T. Chow. 1994. Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J. Biol. Chem. 269:24058-24065.
Loo, Y. M., and T. Melendy. 2004. Recruitment of replication protein A by the papillomavirus E1 protein and modulation by single-stranded DNA. J. Virol. 78:1605-1615.
Masterson, P. J., M. A. Stanley, A. P. Lewis, and M. A. Romanos. 1998. A C-terminal helicase domain of the human papillomavirus E1 protein binds E2 and the DNA polymerase -primase p68 subunit. J. Virol. 72:7407-7419.
Mohr, I. J., R. Clark, S. Sun, E. J. Androphy, P. MacPherson, and M. R. Botchan. 1990. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 250:1694-1699.
Park, P., W. Copeland, L. Yang, T. Wang, M. R. Botchan, and I. J. Mohr. 1994. The cellular DNA polymerase alpha-primase is required for papillomavirus DNA replication and associates with the viral E1 helicase. Proc. Natl. Acad. Sci. USA 91:8700-8704.
Sarafi, T. R., and A. A. McBride. 1995. Domains of the BPV-1 E1 replication protein required for origin-specific DNA binding and interaction with the E2 transactivator. Virology 211:385-396.
Sedman, J., and A. Stenlund. 1996. The initiator protein E1 binds to the bovine papillomavirus origin of replication as a trimeric ring-like structure. EMBO J. 15:5085-5092.
Simmons, D. T., T. Melendy, D. Usher, and B. Stillman. 1996. Simian virus 40 large T antigen binds to topoisomerase I. Virology 222:365-374.
Simmons, D. T., P. W. Trowbridge, and R. Roy. 1998. Topoisomerase I stimulates SV40 T antigen-mediated DNA replication and inhibits T antigen's ability to unwind DNA at nonorigin sites. Virology 242:435-443.
Stenlund, A. 2003. E1 initiator DNA binding specificity is unmasked by selective inhibition of non-specific DNA binding. EMBO J. 22:954-963.
Stenlund, A. 2003. Initiation of DNA replication: lessons from viral initiator proteins. Nat. Rev. Mol. Cell Biol. 4:777-785.
Stewart, L., and J. J. Champoux. 2001. Assaying DNA topoisomerase I relaxation activity. Methods Mol. Biol. 95:1-11.
Sun, Y., H. Han, and D. J. McCance. 1998. Active domains of human papillomavirus type 11 E1 protein for origin replication. J. Gen. Virol. 79:1651-1658.
Thorner, L. K., D. A. Lim, and M. R. Botchan. 1993. DNA-binding domain of bovine papillomavirus type 1 E1 helicase: structural and functional aspects. J. Virol. 67:6000-6014.
Waga, S., and B. Stillman. 1998. The DNA replication fork in eukaryotic cells. Annu. Rev. Biochem. 67:721-751.
Wilson, V. G., M. West, K. Woytek, and D. Rangasamy. 2002. Papillomavirus E1 proteins: form, function, and features. Virus Genes 24:275-290.
Yang, L., I. Mohr, E. Fouts, D. A. Lim, M. Nohaile, and M. Botchan. 1993. The E1 protein of bovine papilloma virus 1 is an ATP-dependent DNA helicase. Proc. Natl. Acad. Sci. USA 90:5086-5090.(Randolph V. Clower, John )
ABSTRACT
The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular DNA replication factors, such as replication protein A or polymerase -primase, to replicate PV genomes. Here, E1 is shown to bind to human topoisomerase I and stimulate its relaxation activity up to sevenfold. The interaction between E1 and topoisomerase I was mapped to the E1 DNA binding domain and C terminus. These findings imply a mechanism for the recruitment of topoisomerase I to PV DNA replication forks and for stimulating topoisomerase I to allow for efficient relaxation of the torsional stress induced by replication fork progression.
TEXT
Papillomaviruses (PVs) are small, nonenveloped, circular DNA viruses (6, 10, 14). The PV E1 protein binds to the PV origin (along with the PV E2 protein), assembles into a hexameric ATP-dependant DNA helicase, and recruits cellular replication factors that work in concert with E1 to replicate the viral genomes (17, 20, 21, 24). E1 has been shown to bind and recruit the cellular factors replication protein A (RPA) and DNA polymerase -primase (2, 6, 12, 13, 15).
One of the essential cellular factors required for PV DNA replication is human topoisomerase I (topoI) (11, 27). topoI is an ATP independent protein that modifies the topology of supercoiled DNA, acting as a swivel to decrease torsional stress on DNA (3, 4, 22). Topoisomerases are important during many cellular processes, such as DNA replication, segregation of daughter chromosomes, modulating nucleosomal structure, transcription, DNA supercoiling, recombination, DNA repair, and genomic stability (8, 18, 25, 26). During the initial stages of DNA replication, the strands of the DNA helix must be separated and the resulting overtwisting of the adjacent DNA must be relieved. Helicases and topoisomerases have been proposed to act together as a "swivelase," instrumental to overcoming these topological obstacles (8). The protein complex that is produced when a helicase and a topoisomerase interact, such as E1-topoI, may be a key step in initiation and play a major role in elongation of DNA replication (8, 19).
The PV E1 protein and human topoI interact. To ascertain whether the PV E1 protein interacts with human topoI, enzyme-linked immunosorbent assay (ELISA)-based protein interaction assays were performed as described previously (12). Purified topoI was immobilized in ELISA plate wells, GST-E1 (human papillomavirus type 11 [HPV-11] or bovine papillomavirus [BPV-1]) was added, and binding was clearly detected (Fig. 1a). Glutathione S-transferase (GST)-YY1, GST, and bovine serum albumin (BSA) did not interact with topoI (Fig. 1a and data not shown). Previous results have demonstrated that GST-E1 also does not interact with other proteins such as SSB or the RPA 32/14 subcomplex (12). topoI was also shown to bind to immobilized GST-E1 and not GST or BSA (Fig. 1b). GST coprecipitations also demonstrated an interaction between E1 and topoI. Glutathione beads were incubated with GST-E1 and 293 cell extract (or purified topoI). Following incubation, the beads were washed in buffer containing 500 mM NaCl and subjected to Western blot analysis (Fig. 1c). These results demonstrate that E1 binds to topoI not only as purified proteins but also within the context of crude cell extracts.
E1 stimulates topoI activity. To determine whether the E1-topoI interaction modulates topoI activity, topoI relaxation assays were performed in the presence and absence of GST-E1 essentially as described previously (22). Increasing amounts of GST-E1 led to a substantial increase in topoI activity (greater than sixfold) (Fig. 2a and b). GST-E1 in the absence of topoI had no intrinsic relaxation activity (Fig. 2a, lane 7). GST, GST-YY1, and additional BSA did not stimulate the relaxation activity of topoI (Fig. 2b). PV origin (BPV-1 and HPV-11) and nonorigin DNA templates were both tested for E1 stimulation of relaxation. All templates showed similar degrees of stimulation by E1, indicating that the presence of a PV origin had no effect on the stimulation of topoI (Fig. 2c and data not shown).
Mapping the E1-topoI interaction. To determine the domains within E1 that interact with topoI, GST-E1 truncation mutants were used in ELISAs. HPV-11 GST-E1 containing amino acids (aa) 1 through 403 of E1 showed a positive interaction with topoI (Fig. 3a, open squares), albeit to a slightly lower level than full-length E1. Conversely, the smaller GST-E1 truncation mutant (aa 1 through 165) showed no significant binding to topoI (Fig. 3a, x). The region between E1 amino acids 165 and 403 encompasses the HPV-11 E1 DNA binding domain (DBD), which consists of amino acids 181 through 353 (1, 23). The homologous BPV-1 E1 DBD (consisting of corresponding amino acids 142 through 308) (5, 9, 16) was also purified and tested for topoI binding using ELISA. The BPV-1 E1 DBD demonstrated a positive interaction, suggesting that the E1 DBD contains a bona fide topoI binding site (Fig. 3a, open triangles, binding site A).
Three amino-terminal HPV-11 GST-E1 truncation mutants were also purified and tested for topoI binding using ELISAs. HPV-11 GST-E1 truncation mutants of aa 310 through 649, aa 346 through 649, and aa 589 through 649, which contain all or part of the core helicase domain (1, 7, 13), all demonstrated a similar positive interaction with topoI (Fig. 3b). From these data, we conclude that the minimal topoI binding site within the C terminus of E1 is within aa 589 through 649 (binding site B). The schematic map of E1 depicts the two domains (sites A and B) within E1 that bind to topoI (Fig. 3c).
E1 truncation mutants and topoI relaxation activity. Plasmid relaxation assays were implemented to assess which of the binding domains affect topoI activity. For each E1 truncation, control reactions were performed in parallel to establish basal topoI relaxation activity and full-length E1's ability to stimulate topoI. As demonstrated above, full-length E1 stimulated topoI approximately sixfold while GST and BSA alone had little effect (Fig. 4a, lanes 8, 2, and 4, respectively). The fragment from aa 1 through 165 E1, which does not bind to topoI, did not stimulate topoI relaxation activity (Fig. 4a, lane 7). The E1 fragment from aa 1 through 403, which binds to topoI, stimulated relaxation activity approximately 3.5-fold (Fig. 4a, lane 10; see also Fig. 4b for quantitation). However, the BPV-1 E1 DBD (Fig. 3c, binding site A) showed no appreciable stimulation of topoI (Fig. 4a, lane 6). This result appears to contrast with the result for the fragment from aa 1 through 403, for which the E1 DBD appeared to be the relevant binding domain. It is possible that aa 1 through 403 may contain amino acid residues outside the E1 DBD that play an ancillary role in the E1-topoI interaction.
Binding site B (the C-terminal E1 fragment, aa 589 through 649) stimulated topoI relaxation activity about half as efficiently as full-length E1 (3.5-fold) (Fig. 4a, lane 5). The two other C-terminal fragments tested (aa 310 through 649 and aa 346 through 649) also stimulated topoI relaxation activity to a similar degree as binding site B (data not shown). All truncations were assayed at the same molar equivalent of full-length E1 (Fig. 4b). The E1 aa 1 through 403 and C-terminal fragments could increase the stimulation of topoI up to 4.5-fold at concentrations at a greater than 1:1 molar ratio (data not shown).
Discussion. In this study, we demonstrated that human topoI binds two distinct regions within the PV E1 protein, the DBD and the C terminus. Using ELISAs and topoI relaxation assays, we demonstrated that of the two minimal regions within E1 that bind topoI, the C-terminal region stimulates topoI relaxation activity as well as the fragment from aa 1 through 403 (which contains binding site A, the DBD), although to a lesser degree. The BPV-1 E1 DBD itself did not stimulate topoI relaxation, indicating that an additional region located within the aa 1 through 403 fragment may be necessary for stimulation. It is unclear at this time how E1 stimulates topoI. Two possibilities are that E1 stimulates the catalytic activity of topoI or that E1 may affect the turnover rate of topoI on DNA. In either case, it is reasonable to suggest that the E1-topoI interaction may be an important aspect of PV DNA replication.
Now that a potential role for the novel E1-topoI interaction has been determined, it will be interesting to ascertain whether topoI stimulates the recruitment of E1 to PV origin sequences and whether E2 plays any role in this interaction.
ACKNOWLEDGMENTS
We thank Jen-Sing Liu, Shu-Ru Kuo, and all members of the Witebsky Center for Microbial Pathogenesis at the University at Buffalo for invaluable scientific discussion. We also thank Te Chung Lee for GST-YY1 protein and J. J. Champoux for the human topoI baculovirus vector. We also thank Dennis McCance for supplying E1 vectors and Meghan Barnhart for her work on this project. Thank you to Yan Hu for purified human topoI preparations. Also, thanks to Philippe Clertant for his help on this project. Thanks to Ed Niles and Mark Sutton for critical reading of the manuscript.
This work was supported by NIH grant R29 GM56406 to T.M. R.V.C. was also supported in part by NIH training grant AI07614.
REFERENCES
Amin, A. A., S. Titolo, A. Pelletier, D. Fink, M. G. Cordingley, and J. Archambault. 2000. Identification of domains of the HPV11 E1 protein required for DNA replication in vitro. Virology 272:137-150.
Bonne-Andrea, C., S. Santucci, P. Clertant, and F. Tillier. 1995. Bovine papillomavirus E1 protein binds specifically DNA polymerase alpha but not replication protein A. J. Virol. 69:2341-2350.
Champoux, J. J. 2001. DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70:369-413.
Champoux, J. J. 2002. A first view of the structure of a type IA topoisomerase with bound DNA. Trends Pharmacol. Sci. 23:199-201.
Chen, G., and A. Stenlund. 1998. Characterization of the DNA-binding domain of the bovine papillomavirus replication initiator E1. J. Virol. 72:2567-2576.
Conger, K. L., J. S. Liu, S. R. Kuo, L. T. Chow, and T. S. Wang. 1999. Human papillomavirus DNA replication. Interactions between the viral E1 protein and two subunits of human DNA polymerase alpha/primase. J. Biol. Chem. 274:2696-2705.
Dixon, E. P., G. L. Pahel, W. J. Rocque, J. A. Barnes, D. C. Lobe, M. H. Hanlon, K. A. Alexander, S. F. Chao, K. Lindley, and W. C. Phelps. 2000. The E1 helicase of human papillomavirus type 11 binds to the origin of replication with low sequence specificity. Virology 270:345-357.
Duguet, M. 1997. When helicase and topoisomerase meet! J. Cell Sci. 110:1345-1350.
Gillitzer, E., G. Chen, and A. Stenlund. 2000. Separate domains in E1 and E2 proteins serve architectural and productive roles for cooperative DNA binding. EMBO J. 19:3069-3079.
Han, Y., Y. M. Loo, K. T. Militello, and T. Melendy. 1999. Interactions of the papovavirus DNA replication initiator proteins, bovine papillomavirus type 1 E1 and simian virus 40 large T antigen, with human replication protein A. J. Virol. 73:4899-4907.
Kuo, S. R., J. S. Liu, T. R. Broker, and L. T. Chow. 1994. Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J. Biol. Chem. 269:24058-24065.
Loo, Y. M., and T. Melendy. 2004. Recruitment of replication protein A by the papillomavirus E1 protein and modulation by single-stranded DNA. J. Virol. 78:1605-1615.
Masterson, P. J., M. A. Stanley, A. P. Lewis, and M. A. Romanos. 1998. A C-terminal helicase domain of the human papillomavirus E1 protein binds E2 and the DNA polymerase -primase p68 subunit. J. Virol. 72:7407-7419.
Mohr, I. J., R. Clark, S. Sun, E. J. Androphy, P. MacPherson, and M. R. Botchan. 1990. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 250:1694-1699.
Park, P., W. Copeland, L. Yang, T. Wang, M. R. Botchan, and I. J. Mohr. 1994. The cellular DNA polymerase alpha-primase is required for papillomavirus DNA replication and associates with the viral E1 helicase. Proc. Natl. Acad. Sci. USA 91:8700-8704.
Sarafi, T. R., and A. A. McBride. 1995. Domains of the BPV-1 E1 replication protein required for origin-specific DNA binding and interaction with the E2 transactivator. Virology 211:385-396.
Sedman, J., and A. Stenlund. 1996. The initiator protein E1 binds to the bovine papillomavirus origin of replication as a trimeric ring-like structure. EMBO J. 15:5085-5092.
Simmons, D. T., T. Melendy, D. Usher, and B. Stillman. 1996. Simian virus 40 large T antigen binds to topoisomerase I. Virology 222:365-374.
Simmons, D. T., P. W. Trowbridge, and R. Roy. 1998. Topoisomerase I stimulates SV40 T antigen-mediated DNA replication and inhibits T antigen's ability to unwind DNA at nonorigin sites. Virology 242:435-443.
Stenlund, A. 2003. E1 initiator DNA binding specificity is unmasked by selective inhibition of non-specific DNA binding. EMBO J. 22:954-963.
Stenlund, A. 2003. Initiation of DNA replication: lessons from viral initiator proteins. Nat. Rev. Mol. Cell Biol. 4:777-785.
Stewart, L., and J. J. Champoux. 2001. Assaying DNA topoisomerase I relaxation activity. Methods Mol. Biol. 95:1-11.
Sun, Y., H. Han, and D. J. McCance. 1998. Active domains of human papillomavirus type 11 E1 protein for origin replication. J. Gen. Virol. 79:1651-1658.
Thorner, L. K., D. A. Lim, and M. R. Botchan. 1993. DNA-binding domain of bovine papillomavirus type 1 E1 helicase: structural and functional aspects. J. Virol. 67:6000-6014.
Waga, S., and B. Stillman. 1998. The DNA replication fork in eukaryotic cells. Annu. Rev. Biochem. 67:721-751.
Wilson, V. G., M. West, K. Woytek, and D. Rangasamy. 2002. Papillomavirus E1 proteins: form, function, and features. Virus Genes 24:275-290.
Yang, L., I. Mohr, E. Fouts, D. A. Lim, M. Nohaile, and M. Botchan. 1993. The E1 protein of bovine papilloma virus 1 is an ATP-dependent DNA helicase. Proc. Natl. Acad. Sci. USA 90:5086-5090.(Randolph V. Clower, John )