Abstract

The overall objective of this proposal is to define the sequence of molecular events that regulate the initiation of SV40 DNA replication. This information is imporant in order to understand the function of an important tumor virus transforming protein and may ultimately be useful in identifying components of host cell replicons as well. We have the following specific aims: 1. To define further the binding of SV40 A protein (T antigen) to the origin of replication, 2. To construct a clone that isolates the minimal origin of replication from other viral regulatory elements, 3. To construct and characterize insertion, deletion, and base substitution mutations in regions of the origin not previously studied, 4. To define further the early replication events in vivo using wild-type and mutant origins, 5. To establish an in vitro system capable of initiating early events in DNA replication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA018808-12
Application #
3165051
Study Section
Virology Study Section (VR)
Project Start
1975-09-01
Project End
1989-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Jackson, P; Mastrangelo, I; Reed, M et al. (1998) Synergistic transcriptional activation of the MCK promoter by p53: tetramers link separated DNA response elements by DNA looping. Oncogene 16:283-92
Anderson, M E; Woelker, B; Reed, M et al. (1997) Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: implications for regulation. Mol Cell Biol 17:6255-64
Ray, S; Anderson, M E; Tegtmeyer, P (1996) Differential interaction of temperature-sensitive simian virus 40 T antigens with tumor suppressors pRb and p53. J Virol 70:7224-7
McVey, D; Woelker, B; Tegtmeyer, P (1996) Mechanisms of simian virus 40 T-antigen activation by phosphorylation of threonine 124. J Virol 70:3887-93
Reed, M; Woelker, B; Wang, P et al. (1995) The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc Natl Acad Sci U S A 92:9455-9
Wang, Y; Schwedes, J F; Parks, D et al. (1995) Interaction of p53 with its consensus DNA-binding site. Mol Cell Biol 15:2157-65
Rainwater, R; Parks, D; Anderson, M E et al. (1995) Role of cysteine residues in regulation of p53 function. Mol Cell Biol 15:3892-903
Stenger, J E; Tegtmeyer, P; Mayr, G A et al. (1994) p53 oligomerization and DNA looping are linked with transcriptional activation. EMBO J 13:6011-20
Wang, P; Reed, M; Wang, Y et al. (1994) p53 domains: structure, oligomerization, and transformation. Mol Cell Biol 14:5182-91
Reed, M; Wang, Y; Mayr, G et al. (1993) p53 domains: suppression, transformation, and transactivation. Gene Expr 3:95-107

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