Base Excision Repair of Oxidative DNA Damage in a Catalase-deficient Mutant of Schizosaccharomyces pombe

Abstract

Base excision repair (BER) is the major pathway to repair oxidized bases in many organisms, but the BER mutants of Schizosaccharomyces pombe are substantially resistant to hydrogen peroxide. To reduce the reactive oxygen species (ROS) scavenging activity in cells, we disrupted a catalase gene, ctt1, in S. pombe. The ctt1 mutant became sensitive to hydrogen peroxide, but had no mutator phenotype. Deletion of the BER genes (nth1, apn1, apn2, or uve1) from ctt1 mutant further increased the hydrogen peroxide sensitivity, indicating that the catalase activity obscures the functions of BER enzymes in vivo. The nth1 and apn2 mutants exhibited a moderate mutator phenotype. Double mutants in both ctt1 and BER genes showed extremely high spontaneous mutation rates, especially in the ctt1/nth1 mutant. Vitamin C relieved the mutator phenotype of the ctt1/nth1 mutant. The ctt1/apn1 and ctt1/uve1 mutants also had high mutation rates, even though each single mutant showed no mutator phenotype. Our results provide evidences that BER enzymes as well as calatase and antioxidant contribute in vivo to avoidance of ROS-induced mutagenesis and cell death.