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ToxSci Advance Access originally published online on June 12, 2003
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Toxicological Sciences 75, 82-88 (2003)
Copyright © 2003 by the Society of Toxicology

GENETIC TOXICOLOGY

Compromised DNA Repair Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System

Xuming Jia and Wei Xiao1

Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5 Canada

ABSTRACT

The RNR3-lacZ genotoxicity testing system was developed based on the induction of a Saccharomyces cerevisiae RNR3-lacZ reporter gene in response to a broad range of DNA-damaging agents. In order to enhance the sensitivity of the RNR3-lacZ system, several deletion mutant strains representing different repair pathways were created and examined for their effects on RNR3-lacZ expression. It was found that inactivation of different DNA repair pathways has profound effects on the DNA damage induction of RNR3 expression. Although deletion of MAG1 in the base excision repair pathway enhances the detection sensitivity to DNA-alkylating agents, and deletion of RAD2 in the nucleotide excision repair pathway enhances the detection sensitivity to ultraviolet and agents that produce bulky lesions, inactivation of genes involved in the recombination repair and postreplication repair variably reduces RNR3-lacZ induction. This study not only helps to establish a more sensitive genotoxicity testing system but also suggests that certain eukaryotic DNA repair pathways are required for gene regulation in response to DNA damage and probably serve as sensors in the signal transduction cascade.

Key Words: RNR3-lacZ; gene regulation; genotoxicity test; sensitivity; DNA repair; eukaryotes.


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