A role for MHR1, a gene required for mitochondrial genetic recombination, in the repair of damage spontaneously introduced in yeast mtDNA

A nuclear recessive mutant in Saccharomyces cerevisiae, mhr1-1, is defectiv e in mitochondrial genetic recombination at 30 degreesC and shows extensive vegetative petite induction by UV irradiation at 30 degreesC or when culti vated at a higher temperature (37 degreesC), It has been postulated that mi tochondrial DNA (mtDNA) is oxidatively damaged by by-products of oxidative respiration. Since genetic recombination plays a critical role in DNA repai r in various organisms, we tested the possibility that MHR1 plays a role in the repair of oxidatively damaged mtDNA using an enzyme assay. mtDNA isola ted from cells grown under standard (aerobic) conditions contained a much h igher level of DNA lesions compared with mtDNA isolated from anaerobically grown cells. Soon after a temperature shift from 30 to 37 degreesC the numb er of mtDNA lesions increased 2-fold in mhr1-1 mutant cells but not in MHR1 cells. Malonic acid, which decreased the oxidative stress in mitochondria, partially suppressed both petite induction and the temperature-induced inc rease in the amount of mtDNA damage in mhr1-1 cells at 37 degreesC, Thus, f unctional mitochondria require active MHR1, which keeps the extent of spont aneous oxidative damage in mtDNA within a tolerable level. These observatio ns are consistent with MHR1 having a possible role in mtDNA repair.