Genetic analysis and DNA repair studies will be used to examine the mechanisms of radiation mutagenesis in the lower eukaryote Saccharomyces cerevisiae. New alleles of genes involved in error-prone repair, such as the RAD6 locus, will be looked for and also searches conducted for new mutations that specifically block frame-shift mutagenesis or RAD6-dependent error-free repair. Genetic experiments will also be used to continue the study of """"""""untargeted"""""""" mutagenesis and the mechanisms by which it occurs. DNA repair studies will examine the relationship between transdimer synthesis and mutagenesis, using a variety of mutant strains thought to be deficient in one or other of these processes, by means of DNA fiber autoradiography and alkaline sucrose gradient sedimentation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021858-11
Application #
3270743
Study Section
Radiation Study Section (RAD)
Project Start
1978-02-01
Project End
1986-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Li, Ziqiang; Zhang, Hong; McManus, Terrence P et al. (2002) hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts. Mutat Res 510:71-80
Lawrence, C W; Maher, V M (2001) Eukaryotic mutagenesis and translesion replication dependent on DNA polymerase zeta and Rev1 protein. Biochem Soc Trans 29:187-91
Lawrence, C W; Maher, V M (2001) Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p. Philos Trans R Soc Lond B Biol Sci 356:41-6
Nelson, J R; Gibbs, P E; Nowicka, A M et al. (2000) Evidence for a second function for Saccharomyces cerevisiae Rev1p. Mol Microbiol 37:549-54
Gibbs, P E; Wang, X D; Li, Z et al. (2000) The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light. Proc Natl Acad Sci U S A 97:4186-91
Lawrence, C W; Gibbs, P E; Murante, R S et al. (2000) Roles of DNA polymerase zeta and Rev1 protein in eukaryotic mutagenesis and translesion replication. Cold Spring Harb Symp Quant Biol 65:61-9
Gibbs, P E; McGregor, W G; Maher, V M et al. (1998) A human homolog of the Saccharomyces cerevisiae REV3 gene, which encodes the catalytic subunit of DNA polymerase zeta. Proc Natl Acad Sci U S A 95:6876-80
Carty, M P; Lawrence, C W; Dixon, K (1996) Complete replication of plasmid DNA containing a single UV-induced lesion in human cell extracts. J Biol Chem 271:9637-47
Nelson, J R; Lawrence, C W; Hinkle, D C (1996) Thymine-thymine dimer bypass by yeast DNA polymerase zeta. Science 272:1646-9
Lawrence, C W; Hinkle, D C (1996) DNA polymerase zeta and the control of DNA damage induced mutagenesis in eukaryotes. Cancer Surv 28:21-31

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