Abstract

The overall goal is to gain an understanding of the role of the alternative excision repair (AER) pathway in the reversal of DNA damage. A great deal of information was gained during the previous funding period which indicates that the AER pathway in the fission yeast Schizosaccharomyces pombe functions in the repair of a diverse group of DNA lesions ranging from UV bi-pyrimidine photoproducts to base mismatches. An emphasis will be placed on the functions of the AER initiating endonuclease Uve1p in S. pombe. In addition, further refinement of the known Uve1p-related pathways identified in the previous project will be pursued. The scope and focus of the present proposal is expanded considerably from the previous emphasis on UV damage. This is necessary in order to begin to define the multiple potential interrelationships between Uve1p and other DNA repair/processing pathways. Biochemical characterization of the components of the AER pathway and potentially related pathways will continue as well as studies aimed at determining the range of organisms which utilize Uve1p-like proteins for DNA repair.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA073041-07
Application #
6628274
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Pelroy, Richard
Project Start
1997-02-01
Project End
2006-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
7
Fiscal Year
2003
Total Cost
$307,800
Indirect Cost

  Institution

Name
Emory University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Bregeon, Damien; Doetsch, Paul W (2006) Assays for transcriptional mutagenesis in active genes. Methods Enzymol 409:345-57
Beljanski, Vladimir; Villanueva, Julie M; Doetsch, Paul W et al. (2005) Marked dependence on carrier-ligand bulk but not on carrier-ligand chirality of the duplex versus single-strand forms of a DNA oligonucleotide with a series of G-Pt(II)-G intrastrand cross-links modeling cisplatin-DNA adducts. J Am Chem Soc 127:15833-42
Beljanski, Vladimir; Marzilli, Luigi G; Doetsch, Paul W (2004) DNA damage-processing pathways involved in the eukaryotic cellular response to anticancer DNA cross-linking drugs. Mol Pharmacol 65:1496-506
Meadows, Kellen L; Song, Binwei; Doetsch, Paul W (2003) Characterization of AP lyase activities of Saccharomyces cerevisiae Ntg1p and Ntg2p: implications for biological function. Nucleic Acids Res 31:5560-7
Doetsch, Paul W (2002) Translesion synthesis by RNA polymerases: occurrence and biological implications for transcriptional mutagenesis. Mutat Res 510:131-40
Doetsch, P W; Morey, N J; Swanson, R L et al. (2001) Yeast base excision repair: interconnections and networks. Prog Nucleic Acid Res Mol Biol 68:29-39
Kaur, B; Doetsch, P W (2000) Ultraviolet damage endonuclease (Uve1p): a structure and strand-specific DNA endonuclease. Biochemistry 39:5788-96
Alleva, J L; Zuo, S; Hurwitz, J et al. (2000) In vitro reconstitution of the Schizosaccharomyces pombe alternative excision repair pathway. Biochemistry 39:2659-66
Alleva, J L; Doetsch, P W (2000) The nature of the 5'-terminus is a major determinant for DNA processing by Schizosaccharomyces pombe Rad2p, a FEN-1 family nuclease. Nucleic Acids Res 28:2893-901
Kaur, B; Fraser, J L; Freyer, G A et al. (1999) A Uve1p-mediated mismatch repair pathway in Schizosaccharomyces pombe. Mol Cell Biol 19:4703-10

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