Abstract

The long term objective of these studies is to define DNA sequences and protein structural elements responsible for polyomavirus transcription and DNA replication and to explain how they function in animal cells. In previous years we have isolated and partially characterized polyomavirus mutants with alterations in the early promoter, in the origin of DNA replication and in the enhancer.
Our specific aims for the forthcoming years are to use these mutants to (a) define structural features of the polyomavirus large T-antigen which are responsible for sequence- specific recognition of the origin; (b) identify domains of the polyomavirus origin which are required for DNA replication and define how they function; (c) define DNA sequence elements within the polyomavirus enhancer which activate transcription and/or replication; (d) characterize cellular proteins which bind to the enhancer, and which are required for DNA replication and/or transcription; and (e) reconstitute in vitro transcription and DNA replication systems which depend upon the enchancer for activity, and determine at what steps the enhancer binding proteins participate.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038538-08
Application #
3176593
Study Section
Virology Study Section (VR)
Project Start
1984-09-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1993-07-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Missouri-Columbia
Department
Type
Schools of Arts and Sciences
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211

  Publications

Xie, An-Yong; Folk, William R (2002) Inhibition of polyomavirus ori-dependent DNA replication by mSin3B. J Virol 76:11809-18
Xie, An-Yong; Bermudez, Vladimir P; Folk, William R (2002) Stimulation of DNA replication from the polyomavirus origin by PCAF and GCN5 acetyltransferases: acetylation of large T antigen. Mol Cell Biol 22:7907-18
Berjanskii, M V; Riley, M I; Xie, A et al. (2000) NMR structure of the N-terminal J domain of murine polyomavirus T antigens. Implications for DnaJ-like domains and for mutations of T antigens. J Biol Chem 275:36094-103
Riley, M I; Yoo, W; Mda, N Y et al. (1997) Tiny T antigen: an autonomous polyomavirus T antigen amino-terminal domain. J Virol 71:6068-74
Guo, W; Tang, W J; Bu, X et al. (1996) AP1 enhances polyomavirus DNA replication by promoting T-antigen-mediated unwinding of DNA. J Virol 70:4914-8
Li, L; Li, B L; Hock, M et al. (1995) Sequences flanking the pentanucleotide T-antigen binding sites in the polyomavirus core origin help determine selectivity of DNA replication. J Virol 69:7570-8
Lednicky, J; Folk, W R (1992) Two synthetic Sp1-binding sites functionally substitute for the 21-base-pair repeat region to activate simian virus 40 growth in CV-1 cells. J Virol 66:6379-90
Kang, S; Folk, W R (1992) Lymphotropic papovavirus transforms hamster cells without altering the amount or stability of p53. Virology 191:754-64
Scanlon, S R; Folk, W R (1991) Nuclease Bal-31 mapping of proteins bound to a tRNA(tyr) gene in SV40 minichromosomes. Nucleic Acids Res 19:7185-92
Tang, W J; Folk, W R (1989) Asp-286----Asn-286 in polyomavirus large T antigen relaxes the specificity of binding to the polyomavirus origin. J Virol 63:242-9

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