Abstract

The long-term goals are to assess the biological consequences of modified DNA bases. The research represents a broad based program employing enzymatic, chemical, genetic, and molecular biological approaches to examine in detail the production and repair/processing off ionizing radiation damage. Substrate specificity studies as well as cloning and wequencing of Escherichia coli repair enzymes are planned. These enzymes will also be used as probes for X-ray-induced DNA damage. Further, unique modified bases are being examined for their ability to serve as replicative breaks in vitro and lethal and/or for mutagenic lesions in vivo. In addition, the effect of various E. coli repair proteins on the processing of unique lesions will be measured by transfecting phage DNA containing these lesions into E. coli mutants defective in particular DNA repair-associated gene products. Lastly, the function of the bacteriophage T4 uvsY and uvsW genes, that are involved in genetic recombination and error prone mutagenesis, are being studied. Ionizing radiation produces a spectrum of DNA damages and the present studies are designed to examine the potential of unique lesions to produce lethal, mutagenic and therefore presumably carcinogenic endpoints.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA033657-09
Application #
3482282
Study Section
Radiation Study Section (RAD)
Project Start
1982-04-01
Project End
1992-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405

  Publications

Wallace, Susan S (2013) DNA glycosylases search for and remove oxidized DNA bases. Environ Mol Mutagen 54:691-704
Faucher, Frédérick; Wallace, Susan S; Doublié, Sylvie (2009) Structural basis for the lack of opposite base specificity of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase. DNA Repair (Amst) 8:1283-9
Yang, Ning; Chaudhry, M Ahmad; Wallace, Susan S (2006) Base excision repair by hNTH1 and hOGG1: a two edged sword in the processing of DNA damage in gamma-irradiated human cells. DNA Repair (Amst) 5:43-51
Bandaru, Viswanath; Blaisdell, Jeffrey O; Wallace, Susan S (2006) Oxidative DNA glycosylases: recipes from cloning to characterization. Methods Enzymol 408:15-33
Watanabe, Takashi; Blaisdell, Jeffrey O; Wallace, Susan S et al. (2005) Engineering functional changes in Escherichia coli endonuclease III based on phylogenetic and structural analyses. J Biol Chem 280:34378-84
Bandaru, Viswanath; Cooper, Wendy; Wallace, Susan S et al. (2004) Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damage. Acta Crystallogr D Biol Crystallogr 60:1142-4
Yang, Ning; Galick, Heather; Wallace, Susan S (2004) Attempted base excision repair of ionizing radiation damage in human lymphoblastoid cells produces lethal and mutagenic double strand breaks. DNA Repair (Amst) 3:1323-34
Doublie, Sylvie; Bandaru, Viswanath; Bond, Jeffrey P et al. (2004) The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity. Proc Natl Acad Sci U S A 101:10284-9
Kathe, Scott D; Shen, Guang-Ping; Wallace, Susan S (2004) Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts. J Biol Chem 279:18511-20
Wallace, Susan S; Bandaru, Viswanath; Kathe, Scott D et al. (2003) The enigma of endonuclease VIII. DNA Repair (Amst) 2:441-53

Showing the most recent 10 out of 54 publications