Curriculum Vitae
Michael R. Botchan

Title: Professor

Birthdate: July 13, 1945

Birthplace: Brooklyn, New York

Education:

New York University, New York, NY B.A. 1967 Biology

University of California, Berkeley, CA Ph.D. 1972 Biophysics

Cold Spring Harbor Laboratory, NY Postdoc 1972-74

Research and Professional Experience:

Senior ScientistCold Spring Harbor Laboratory 1974 - 1980
Cold Spring Harbor, New York

Adjunct Associate Department of Microbiology 1977 - 1979
Professor State University of New York
Stony Brook, New York

Associate Professor Department of Molecular Biology 1980 - 1984
University of California
Berkeley, California

Professor Department of Molecular and Cell Biology 1984 - present
University of California
Berkeley, California

Major Research Interest:
DNA virus transformation; eukaryotic DNA replication and transcription; recombination in somatic cells

Honors: Phi Beta Kappa; Damon Runyon-Walter Winchell Research Fellow, 1974; NIH Merit Award, 1987; American Society of Microbiology Division S Lecturer; Chairman, Scientific Advisory Committee, Damon Runyon-Walter Winchell Cancer Research Fund, 1992

Appointments and Professional Service:

Member: National Institutes of Health Virology Study Section, 1986-1991
American Cancer Society Advisory Committee on Cell Biology and Microbiology, 1978 - 1981
American Cancer Society Advisory Committee on Nucleic Acids and Proteins, 1986 - 1990
American Cancer Society California Division: Post-doctoral Fellowship Committee, 1986 - 1989
Damon Runyon-Walter Winchell Cancer Research Fund: Scientific Advisory Committee (SAC), 1989 - 1992Editor: Plasmid, 1986 - present
Editorial Boards: Journal of Virology, 1984-1990
Molecular and Cellular Biology, 1985-1991
Oncogene, 1987-1991

Publications:

  1. Hearst, J. E. and M. Botchan. 1970. The eukaryotic chromosome. Ann. Rev. Biochem. 39: 151-182.
  2. Botchan, M., R. Kram, C. W. Schmid and J. E. Hearst. 1971. Isolation and chromosomal localization of highly repeated DNA sequences in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 68: 1125-1129.
  3. Kram, R., M. Botchan and J. E. Hearst. 1972. Arrangement of the highly reiterated DNA sequence in the centric heterochromatin of Drosophila melanogaster. Evidence for interspersed spacer DNA. J. Mol. Biol. 64: 103-117.
  4. Carroll, D. and M. R. Botchan. 1972. Competition between pentalysine and actinomycin D for binding to DNA. Biochem. Biophys. Res. Commun. 46: 1681-1687.
  5. Botchan, M. R. and R. Kram. 1972. "Involvement of microtubule assembly in the morphological differentiation of D.melanogaster primary embryonic cells in vitro." Cell Differentiation. Harris, Allen and Vita ed. Munksgaard. Copenhagen.
  6. Hearst, J. E. and M. Botchan. 1973. Deoxyribonucleic acid renaturation kinetics and hybridization. Accts. Chem. Res. 6: 293-298.
  7. Hearst, J. E., M. Botchan, R. Kram and E. Beals. 1973. The use of buoyant density profiles in determining the length and spacing of repeated sequences in DNA. Biochim. Biophus. Acta. 294: 173-183.
  8. Botchan, M. R. 1974. Bovine satellite I DNA consists of repetitive units 1400 base pairs in length. Nature. 251: 288-292.
  9. Botchan, M., G. McKenna and P. A. Sharp. 1974. Cleavage of mouse DNA by a restriction enzyme as a clue to the arrangement of genes. Cold Spring Harbor Symp. Quant. Biol. 38: 383-395.
  10. Botchan, M., B. Ozanne, B. Sugden, S. P.A. and J. Sambrook. 1974. Viral DNA in transformed cells. III. The amounts of different regions of the SV40 genome present in a line of transformed mouse cells. Proc. Natl. Acad. Sci. USA. 71: 4183-4187.
  11. Sambrook, J., M. Botchan, P. Gallimore, B. Ozanne Pettersson, U., J. Williams and P. A. Sharp. 1975. Viral DNA sequences in cells transformed by simian virus 40, adenovirus type 2 and adenovirus type 5. Cold Spring Harbor Symp. Quant. Biol. 39: 615-632.
  12. Botchan, M., B. Ozanne, B. Sugden, P. A. Sharp and J. Sambrook. 1975. Characterization of SV40 DNA rescued from transformed mouse cells. Cold Spring Harbor Symp. Quant. Biol. 39: 95-99.
  13. Bukhari, A. I., S. Froshauer and M. Botchan. 1976. Ends of bacteriophage mu DNA. Nature. 264: 580-583.
  14. Botchan, M., W. Topp and J. Sambrook. 1976. The arrangement of simian virus 40 sequences in the DNA of transformed cells. Cell. 9: 269-287.
  15. Sambrook, J., D. Galloway, W. Topp and M. Botchan. 1977. "The arrangement of viral DNA sequences in the genomes of cells transformed by SV40 or adenovirus 2." International Cell Biology. Porter ed. Rockefeller University Press.
  16. Steinberg, B., R. Pollack, W. Topp and M. Botchan. 1978. Isolation and characterization of T antigen-negative revertants from a line of transformed rat cells containing one copy of the SV40 genome. Cell. 13: 19-32.
  17. Kucherlapati, R., S. P. Hwang, N. Shimizu, J. K. McDougall and M. R. Botchan. 1978. Another chromosomal assignment for a simian virus 40 integration site in human cells. Proc. Natl. Acad. Sci. USA. 75: 4460-4464.
  18. Graessmann, A., M. Graessmann, W. C. Topp and M. Botchan. 1979. Retransformation of a simian virus 40 revertant cell line, which is resistant to viral and DNA infections, by microinjection of viral DNA. J. Virol. 32: 989-994.
  19. Botchan, M., W. Topp and J. Sambrook. 1979. Studies on simian virus 40 excision from cellular chromosomes. Cold Spring Harbor Symp. Quant. Biol. 43: 709-719.
  20. Schaffner, W., W. Topp and M. Botchan. 1979. "Movement of foreign DNA into and out of somatic cell chromosomes by linkage to SV40." Specific Eukaryotic Genes. Munksgaard. Copenhagen.
  21. Sambrook, J., R. Greene, J. Stringer, T. Mitchison, S.-L. Hu and M. Botchan. 1980. Analysis of the sites of integration of viral DNA sequences in rat cells transformed by adenovirus 2 or SV40. Cold Spring Harbor Symp. Quant. Biol. 44: 569-584.
  22. Botchan, M., J. Stringer, T. Mitchison and J. Sambrook. 1980. Integration and excision of SV40 DNA from the chromosome of a transformed cell. Cell. 20: 143-152.
  23. Hanahan, D., D. Lane, L. Lipsich, M. Wigler and M. Botchan. 1980. Characteristics of an SV40-plasmid recombinant and its movement into and out of the genome of a murine cell. Cell. 21: 127-139.
  24. Lusky, M. and M. R. Botchan. 1981. Inhibition of SV-40 replication in simian cells by specific pBR322 DNA sequences. Nature. 293: 79-81.
  25. Bullock, P. and M. Botchan. 1982. "Molecular events in the excision of SV40 DNA from the chromosomes of cultured mammalian cells." Gene Amplification. Schimke ed. Cold Spring Harbor Press. Cold Spring Harbor, New York.
  26. Conrad, S. E., C.-P. Liu and M. R. Botchan. 1982. Fragment spanning the SV40 replication origin is the only DNA sequence required in cis for viral excision. Science. 218: 1223-1225.
  27. Lusky, M., L. Berg and M. Botchan. 1982. "Enhancement of Tk transformation by sequences of bovine papilloma virus." Eukaryotic Viral Vectors. Gluzman ed. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.
  28. Kriegler, M. and M. Botchan. 1982. "A retroviral long terminal repeat contains a new type of eukaryotic regulatory element." Eukaryotic Viral Vectors. Gluzman ed. Cold Spring Harbor Laboratory, New York. Cold Spring Harbor, New York.
  29. Conrad, S. E. and M. R. Botchan. 1982. Isolation and characterization of human DNA fragments with nucleotide sequence homologies with the simian virus 40 regulatory region. Mol. Cell. Biol. 2: 949-965.
  30. Kriegler, M., C. Perez, C. Hardy and M. Botchan. 1983. "Viral integration and early gene expression both affect the efficiency of SV40 induced transformation of murine cells: Biochemical and biological characterizaiton of an SV40 retrovirus." The Cancer Cell. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.
  31. Kriegler, M., C. Perez and M. Botchan. 1983. "Promoter substitution and enhancer augmentation increases the penetrance of the SV40 A gene to levels comparable to that of the Harvey murine sarcoma virus ras gene in morphologic transformation." Gene Expression. Hamer and Rosenberg ed. Alan R. Liss. New York.
  32. Kriegler, M. and M. Botchan. 1983. Enchanced transformation by a simian virus 40 recombinant virus containing a Harvey murine sarcoma virus long terminal repeat. Mol. Cell. Biol. 3: 325-339.
  33. Calos, M., J. S. Lebkowski and M. R. Botchan. 1983. High mutation frequency in DNA transfected into mammalian cells. Proc. Natl. Acad. Sci. USA. 80: 3015-3019.
  34. Lusky, M., L. Berg, H. Weiher and M. Botchan. 1983. Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit. Mol. Cell. Biol. 3: 1108-1122.
  35. Lusky, M., H. Weiher, M. Kriegler, L. Berg and M. Botchan. 1983. "The anatomy of the bovine papilloma virus activator and the relationship between enhancers of transformation and activators of transcription." Controlling Elements in Eukaryotic Transcription. Gluzman ed. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.
  36. Miller, J., P. Bullock and M. Botchan. 1984. SV40 T-antigen is required for viral excision from chromosomes. Proc. Natl. Acad. Sci. USA. 81: 7534-7538.
  37. Lebkowski, J., M. Botchan and M. Calos. 1984. "Cellular responses to DNA damage." UCLA Symposium on Molecular and Cellular Biology. Friedberg and Bridges ed. Alan R. Liss, Inc. New York.
  38. Bullock, P., W. Forrester and M. Botchan. 1984. DNA sequence studies of simian virus 40 chromosomal excision and integration in rat cells. J. Mol. Biol. 174: 55-84.
  39. Kriegler, M., C. Perez, C. Hardy and M. Botchan. 1984. Transformation mediated by the SV40 T antigens: Separation of the overlapping SV40 early genes with a retroviral vector. Cell. 38: 483-491.
  40. Lusky, M. and M. R. Botchan. 1984. Characterization of the bovine papilloma virus plasmid maintenance sequences. Cell. 36: 391-401.
  41. Weiher, H. and M. Botchan. 1984. An enhancer sequence from bovine papilloma virus DNA consists of two essential regions. Nucleic Acids Res. 12: 2901-2916.
  42. Bullock, P., J. J. Champoux and M. Botchan. 1985. SV40 excisional recombination cross-over points are associated with rat liver topoisomerase I cleavage sites in vitro. Science. 230: 954-958.
  43. Robbins, P. and M. Botchan. 1985. "Regulation of enhancer-promoter interactions by SV40 T antigen." Sequence Specificity in Transcription and Translation. Calendar and Gold ed.
  44. Singh, K., S. Saragosti and M. Botchan. 1985. Isolation of cellular genes differentially expressed in mouse NIH 3T3 cells and a Simian Virus 40-transformed derivative: Growth-specific expression of VL30 genes. Mol. Cell. Biol. 5: 2590-2598.
  45. Perez, C. F., M. R. Botchan and C. A. Tobias. 1985. DNA-mediated gene transfer efficiency is enhanced by ionizing and ultraviolet irradiation of rodent cells in vitro. Radiation Res. 104: 200-213.
  46. DuBridge, R. B., M. Lusky, M. R. Botchan and M. P. Calos. 1985. Amplification of a bovine papilloma virus-simian virus 40 chimaera. J. Virol. 56: 625-627.
  47. Lusky, M. and M. R. Botchan. 1985. Genetic analysis of bovine papillomavirus type 1 trans-acting replication factors. J. Virol. 53: 955-965.
  48. Robbins, P. and M. Botchan. 1985. "Promoter specificity of the SV40 enhancer: Activation by T antigen." Eukaryotic Transcription: The Role of Cis- and Trans-acting Elements in Initiation. Gluzman ed. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.
  49. Singh, K., M. Carey, S. Saragosti and M. R. Botchan. 1985. SV40 transformed mouse cells express enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats. Nature. 314: 553-556.
  50. Berg, L. J., K. Singh and M. Botchan. 1986. Complementation of a BPV low copy number mutant: Evidence for a temporal requirement of the complementing gene. Mol. Cell. Biol. 6: 859-869.
  51. Broker, T. R. and M. Botchan. 1986. "Papillomaviruses: retrospectives and prospectives." Cancer Cells 4. DNA Tumor Viruses: Control of Gene Expression and Replication. M. Botchan, Grodzicker and Sharp ed. Cold Spring Harbor Laboratory. New York.
  52. Lusky, M. and M. R. Botchan. 1986. Transient replication of bovine papilloma virus type 1 plasmids: cis and trans requirements. Proc. Natl. Acad. Sci. USA. 83: 3609-3613.
  53. Robbins, P., D. C. Rio and M. R. Botchan. 1986. Trans activation of the simian virus 40 enhancer. Mol. Cell. Biol. 6: 1283-1295.
  54. Bullock, P., J. Miller and M. Botchan. 1986. Effects of poly[d(pGpT) . d(pApC)] and poly[d(pCpG) . d(pCpG)] repeats on homologous recombination in somatic cells. Mol. Cell. Biol. 6: 3948-3953.
  55. Lusky, M. and M. R. Botchan. 1986. A bovine papillomavirus type 1-encoded modulator function is dispensable for transient viral replication but is required for establishment of the stable plasmid state. J. Virol. 60: 729-742.
  56. Carey, M. F., K. Singh, M. Botchan and N. R. Cozzarelli. 1986. Induction of specific transcription by RNA polymerase III in transformed cells. Mol. Cell. Biol. 6: 3068-3076.
  57. Berg, L., M. Lusky, A. Stenlund and M. R. Botchan. 1986. Repression of bovine papilloma virus replication is mediated by a virally encoded trans-acting factor. Cell. 46: 753-762.
  58. Botchan, M. and T. Broker. 1986. "Papillomaviruses: Current overview and future directions." Cancer Cells 4/DNA Tumor Viruses: Control of Gene Expression and Replication. Botchan, Grodzicker and Sharp ed. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.
  59. Botchan, M., L. Berg, J. Reynolds and M. Lusky. 1986. "The bovine papillomavirus replicon." Papillomaviruses. Howley ed. John Wiley and Sons. New York.
  60. Stenlund, A., G. L. Bream and M. R. Botchan. 1987. A promoter with an internal regulatory domain is part of the origin of replication in BPV-1. Science. 236: 1666-1671.
  61. Naruto, M. and M. Botchan. 1987. "The expression and separation of overlapping transforming genes from BPV-1 using an infectious retroviral vector system." Gene Transfer Vectors for Mammalian Cells. Miller and Calos ed. Cold Spring Harbor Laboratory. Cold Spring Harbor, NY.
  62. Gish, W. and M. R. Botchan. 1987. Simian virus 40-transformed human cells that express large T antigens defective for viral DNA replication. J. Virol. 61: 2864-2876.
  63. Thorner, L., N. Bucay, J. Choe and M. Botchan. 1988. The product of the bovine papillomavirus type 1 modulator gene (M) is a phosphoprotein. J. Virol. 62: 2474-2482.
  64. Li, R., J. Knight, G. Bream, A. Stenlund and M. Botchan. 1989. Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes Dev. 3: 510-526.
  65. Choe, J., P. Vaillancourt, A. Stenlund and M. Botchan. 1989. Bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cDNAs. J. Virol. 63: 1743-1755.
  66. Vaillancourt, P., T. Nottoli, J. Choe and M. R. Botchan. 1990. The E2 transactivator of bovine papillomavirus type I is expressed from multiple early promoters. J. Virol. 64: 3927-3937.
  67. Yang, L. and M. Botchan. 1990. Replication of bovine papillomavirus type-1 DNA initiates within an E2 responsive enhancer element. J. Virol. 64: 5903-5911.
  68. Stenlund, A. and M. Botchan. 1990. The E2 transactivator can act as a repressor by interfering with a cellular transcription factor. Genes Dev. 4: 123-136.
  69. 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.
  70. Sun, S., L. Thorner, M. Lentz, P. MacPherson and M. Botchan. 1990. Identification of a 68 kDa nuclear ATP-binding phosphoprotein encoded by bovine papillomavirus type 1. J. Virol. 64: 5093-5105.
  71. Knight, J., R. Li and M. Botchan. 1991. The activation domain of the Bovine Papillomavirus E2 protein mediates association of DNA bound dimers to form DNA loops. Proc. Natl. Acad. Sci. USA. 88: 3204-3208.
  72. Li, R., J. D. Knight, S. P. Jackson, R. Tjian and M. R. Botchan. 1991. Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription. Cell. 65: 493-505.
  73. Yang, L., R. Li, I. J. Mohr, R. Clark and M. R. Botchan. 1991. BPV-1 replication in vitro is activated by the transcription factor E2. Nature. 353: 628-633.
  74. Bream, G. L., P. Vaillancourt and M. R. Botchan. 1992. A constitutive enhancer in the bovine papillomavirus upstream regulatory region shares genetic elements with the viral P1 promoter. J. Virol. 66: 7319-7327.
  75. Yang, L., I. Mohr, R. Li, T. Nottoli, S. Sun and M. Botchan. 1992. The transcription factor E2 regulates BPV-1 DNA replication in vitro by direct protein-protein interaction. Cold Spring Harbor Symp. Quant. Biol. 56: 335-346.
  76. Maulbecker, C., I. Mohr, Y. Gluzman, J. Bartholomew and M. Botchan. 1992. A deletion in the SV40 large T antigen impairs lytic replication in monkey cells in vivo, but enhances replication in vitro: a new complementation group in T antigen. J. Virol. 66: 2195-2207.
  77. Kim, S.-J., U. S. Onwuta, Y. I. Lee, R. Li, M. R. Botchan and P. D. Robbins. 1992. The retinoblastoma gene product regulates Sp1-mediated transcription. Mol. Cell. Biol. 12: 2455-2463.
  78. Yang, L., I. Mohr, E. Fouts, D. A. Lim, M. Nohaile and M. Botchan. 1993. The E1 Protein of the papillomavirus BPV-1 is an ATP dependent DNA helicase. Proc. Natl. Acad. Sci. USA. 90: 5086-5090.
  79. Yang, L., E. Fouts and M.R. Botchan. 1993. Site-specific DNA-binding proteins important for replication and transcription have multiple activities. Cold Spring Harbor Symp. Quant. Biol. 58: 403-413.
  80. Li, R. and M. R. Botchan. 1993. The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication. Cell. 73: 1207-1221.
  81. Thorner, L., D. 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.
  82. Lentz, M. R., D. Pak, I. Mohr and M. R. Botchan. 1993. The E1 replication protein of bovine papillomavirus type-1 contains an extended nuclear localization signal that includes by a p34cdc2 phosphorylation site. J. Virol. 67: 1414-1423.
  83. . MacPherson, Paul, Lauren Thorner and Michael R. Botchan. 1994. The bovine papilloma virus E1 protein has ATPase activity essential to viral DNA replication and efficient transformation in cells. Virology 204: 403-408.
  84. Kaufman, Paul D. and Michael R. Botchan. 1994. Assembly of nucleosomes: do multiple assembly factors mean multiple mechanisms? Curr. Op. in Gen. & Dev. 4: 229-235.
  85. Park, Peter, Liu Yang, T. Wang and M. Botchan. 1994. The cellular DNA polymerase alpha-primase is required for papilloma replication, and it interacts with the viral E1 helicase, Proc. Natl. Acad. Sci. USA 91: 8700-8704.
  86. Li, Rong and Michael R. Botchan. 1994. Acidic transcription factors alleviate nucleosome-mediated repression of BPV-1 DNA replication, Proc. Natl. Acad. Sci. USA 91: 7051-7055.
  87. Russell, Jackie A. and Michael R. Botchan. 1995. Cis-acting components of Human Papillomaviruses. J. Virol. 69: 651-660.
  88. Wyman, C. and M. Botchan. 1995. A familiar ring to DNA polymerase processivity. Curr. Biol. 5: 335-337.
  89. Mendoza, R., L. Gandhi, and M.R. Botchan. 1995. The E1 recognition sequences in the BPV-1 Origin of DNA replication: Cooperativity between half-sites of the inverted repeats. J. Virol. 69:3789-3798.
  90. Ehrenhofer-Murray, A.E., M. Gossen, D.T.S. Pak, M.R. Botchan, and J. Rine. 1995. Separation of origin recognition complex functions by cross-species complementation. Science 270:1671-1674.
  91. Gossen, M., D.T.S. Pak, S.K. Hansen, J.K. Acharya, and M.R. Botchan. 1995. A Drosophila homolog of the yeast origin recognition complex. Science 270:1674-1677.
  92. Ferguson, M.K. and M.R. Botchan. 1996. A genetic analysis of the activation domain of the bovine papillomavirus protein E2: Its role in transcription and replication. J. Virol. 70:4193-4199.
  93. Botchan, M.R. 1996. Coordinating DNA replication with cell division: Current status of the licensing concept. (Commentary). Proc. Natl. Acad. Sci. 93:9997-10,000.
  94. Chesnokov, I., W.M. Chu, M. Botchan, and C. Schmid. 1996. p53 inhibits polIII transcription in a promoter specific way. Mol. Cell. Biol. 16:7084-7088.
  95. Lehman, C.W., D.S. King, and M.R. Botchan. 1997. A papillomavirus E2 phosphorylation mutant exhibits normal transient replication and transcription but is defective in transformation and plasmid retention. J. Virol. 71:3652-3665.
  96. Abramova, N. A., J. Russell, M. Botchan and R. Li. 1997. Interaction between replication protein A and p53 is disrupted following UV damage in a DNA repair-dependent manner. Proc. Natl. Acad. Sci. USA 94:7186-7191.
  97. Pak, D.T.S., M. Pflumm, I. Chesnokov, D.W. Huang, R. Kellum, P. Romanowski, and M.R. Botchan. 1997. Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes. Cell 91:311-323.
  98. Lim, D., M. Gossen, C. Lehman, and M. Botchan. 1997. Competition for DNA binding sites between the short and long forms of E2 dimers underlies repression in BPV-1 DNA replication control. J. Virol.: in press.
  99. Lehman, C.W. and M.R. Botchan. 1997. Segregation of viral plasmids depends on tethering to chromosomes and is regulated by phosphorylation. Science: submitted.




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