A NUCLEAR MUTATION DEFECTIVE IN MITOCHONDRIAL RECOMBINATION IN YEAST

Homologous recombination (crossing over and gene conversion) is genera lly essential for heritage and DNA repair, and occasionally causes DNA aberrations, in nuclei of eukaryotes, However, little is known about the roles of homologous recombination in the inheritance and stability of mitochondrial DNA which is continuously damaged by reactive oxygen species, byproducts of respiration, Here, we report the first example of a nuclear recessive mutation which suggests an essential role for homologous recombination in the stable inheritance of mitochondrial DN A, For the detection of this class of mutants, we devised a novel proc edure, 'mitochondrial crossing in haploid', which has enabled us to ex amine many mutant clones. Using this procedure, we examined mutants of Saccharomyces cerevisiae that showed an elevated UV induction of resp iration-deficient mutations. We obtained a mutant that was defective i n both the omega-intron homing and Endo.SceI-induced homologous gene c onversion, We found that the mutant cells are temperature sensitive in the maintenance of mitochondrial DNA, A tetrad analysis indicated tha t elevated UV induction of respiration-deficient mutations, recombinat ion deficiency and temperature sensitivity are all caused by a single nuclear mutation (mhr1) on chromosome XII. The pleiotropic characteris tics of the mutant suggest an essential role for the MHR1 gene in DNA repair, recombination and the maintenance of DNA in mitochondria.