Simian virus 40 (SV40) will be used as a model cellular replicon in the study of both normal and aberrant DNA replication in mammalian cells. This work will focus on perturbations in DNA synthesis due to cellular stressors such as cytotoxic drugs. DNA damage and nucleotide pool imbalance. Studies of abnormal SV40 DNA replication in this laboratory have provided significant new information about both normal and abnormal DNA replication. Since the understanding of each can be improved by a better understanding of the other, certain aspects of normal DNA replication will continue to be a part of these investigations. Early studies in this laboratory with cytotoxic topoisomerase inhibitors have given clues to the nature and location of the swivel enzyme which removes superhelical density generated by moving replication forks, provided convincing evidence that a type II topoisomerase is required to separate newly replicated daughter chromosomes in mammalian cells, and provided evidence for the mechanism of sister chromatid exchange. These lines of investigation will be extended and several other aspects of aberrant DNA replication will be studied during the proposed funding period.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA045208-05
Application #
3458265
Study Section
Experimental Virology Study Section (EVR)
Project Start
1987-07-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1993-05-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Permana, P A; Ho, D K; Cassady, J M et al. (1994) Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. Cancer Res 54:3191-5
Permana, P A; Snapka, R M (1994) Aldehyde-induced protein-DNA crosslinks disrupt specific stages of SV40 DNA replication. Carcinogenesis 15:1031-6
Snapka, R M; Permana, P A (1993) SV40 DNA replication intermediates: analysis of drugs which target mammalian DNA replication. Bioessays 15:121-7
Snapka, R M; Shin, C G; Permana, P A et al. (1991) Aphidicolin-induced topological and recombinational events in simian virus 40. Nucleic Acids Res 19:5065-72
Shin, C G; Snapka, R M (1990) Patterns of strongly protein-associated simian virus 40 DNA replication intermediates resulting from exposures to specific topoisomerase poisons. Biochemistry 29:10934-9
Shin, C G; Strayer, J M; Wani, M A et al. (1990) Rapid evaluation of topoisomerase inhibitors: caffeine inhibition of topoisomerases in vivo. Teratog Carcinog Mutagen 10:41-52
Shin, C G; Snapka, R M (1990) Exposure to camptothecin breaks leading and lagging strand simian virus 40 DNA replication forks. Biochem Biophys Res Commun 168:135-40
Snapka, R M; Powelson, M A; Strayer, J M (1988) Swiveling and decatenation of replicating simian virus 40 genomes in vivo. Mol Cell Biol 8:515-21