Two distinct mechanisms for deletion in mitochondrial DNA of Schizosaccharomyces pombe mutator strains : Slipped mispairing mediated by direct repeats and erroneous intron splicing

Mutator strains of the fission yeast Schizosaccharomyces pombe produce mitochondrial respiratory deficient mutants at a high rate, and roughly 20% of these mutants carry deletions in the range of 50 to 1500 base-pairs. To elucidate the mechanism of deletion we have sequenced ten deletion mutants in the mosaic gene encoding apocytochrome b ( cob) and three in the split gene coding for the first subunit of cytochrome c oxidase ( cox1). Of 13 deletions, ten are correlated with the presence of direct repeats, which could promote deletions by slipped mispairing during DNA replication. In some of these mutants, the termini are located in possible DNA secondary structures. In three independently isolated mutants with identical deletions in the cob gene, the 5′ deletion endpoint coincides with the 3′ splice point of the intron, whereas the 3′ endpoint of the deletion exhibits pronounced homology with the 5′ splice point of the intron. This result suggests that these deletions might be initiated by erroneous RNA splicing.