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Greg A. Freyer, Ph.D.

Associate Professor

E-mail: gaf1@columbia.edu

DNA repair and its regulation

Our research interest is the study of DNA repair using the fission yeast Schizosaccharomyces pombe as our model system. S. pombe has two DNA excision repair pathways. The first is nucleotide excision repair which was first characterized in E. coli but has been described in virtually every organism. The second repair process, named UVDR for UV damage repair, was discovered in our laboratory and is specific for repair of UV photoproducts. The repair process is initiated by cleavage by 5' to cyclobutane pyrimidine dimers and (6-4) pyrimidine pyrimidones by an enzyme which we have isolated named UVDE for UV damage endonuclease. Part of our effort is aimed at determining the mechanism for UVDR.

When S. pombe cells experience DNA damage the cells arrest growth in the G2 phase of the cell cycle, a process regulated by several known genes. In response to DNA damage UVDE levels elevate and UVDR regulation is mediated through the G2 checkpoint control genes. Therefore, we can use UVDE regulation to study how the G2 checkpoint proteins function. We recently isolated a new gene, rad12, which regulates UVDE but is not a G2 checkpoint gene. The rad12 gene is the S. pombe homologue of the human Bloom's syndrome. Individual with this syndrome have very high rates of cancer. An understanding of how rad12 functions in S. pombe should lead to major insights into how it functions in human cells.

Selected Publications
Bowman, K.K., Sidik, K., Smith, C.A., Taylor, J.S., Doetsch, P.W., and Freyer, G.A. (1994) A new ATP-independent DNA endonuclease from Schizosaccharomyces pombe that recognizes cyclobutane pyrimidine dimers and 6-4 photoproducts. Nucleic Acids Res. 22:3026-2032.

Freyer, G.A., Davey, S., Ferrer, J.V., Martin, A.M., Beach, D., and Doetsch, P.W. (1995) An alternative DNA excision repair pathway. Mol. Biol. Cell 15:4572-4577.

Sidik, K., Lieberman, H.B. and Freyer, G.A. (1992) Repair of DNA damage by UV light and ionizing radiation by cell-free extracts prepared from Schizosaccharomyces pombe. Proc. Natl. Acad. Sci. U.S.A. 89:12112-12116.

Freyer, G.A., Palmer, D.A., Yu, Y., Miller, R.C. and Pandita, T.K. (1996) Neoplastic transformation of mouse C3H10T1/2 cells following exposure to neutrons does not involve mutation of ras gene as analyzed by SSCP and cycle sequencing. Mutation Res. 357:237-244.

Davey, S., Nass, M.L., Ferrer, J.V., Sidik, K., Eisenberger, A., Mitchell, D.L., and Freyer, G.A. (1997) The fission yeast UVDR DNA repair pathway is inducible. in press in Nucleic Acids Res.

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