Involvement of the MRE2 gene of yeast in formation of meiosis-specific double-strand breaks and crossover recombination through RNA splicing.

Abstract

The mre2 mutant of Saccharomyces cerevisiae is defective in meiotic recombination and produces inviable spores, but the sensitivities to DNA damaging agents, methyl methanesulphonate and ultraviolet light are not altered by the mutation. Mre2 has two copies of RNA recognition motif (RRM), suggesting its participation in RNA metabolism in meiosis. An amino acid substitution in the N-terminal RRM of Mre2 confers a meiotic recombination defect. Using this mre2N strain, the MER2 gene was isolated as a multi-copy suppressor of the recombination defect. Meiosis-specific splicing of MER2 pre-mRNA was impaired in the mre2 deletion (mre2delta) mutant. The mre2delta mutant was defective in the formation of meiosis-specific double-strand breaks (DSBs) and crossover and noncrossover recombinants. When the chromosomal MER2 gene was replaced with the intronless derivative of MER2 gene, cMER2, the formation of DSBs and of noncrossover recombinants were restored in the mre2delta mutant. However, the amount of crossover recombinants produced in the mre2delta cMER2 strain was approximately 30% that in the wild-type. In addition, the mre2delta cMER2 mutant was defective in chromosome segregation and in viable spore formation. Mre2 participates in the formation of DSBs through meiosis-specific splicing of MER2 pre-mRNA. Besides, Mre2 is also involved in crossover recombination, possibly through splicing of RNA from another gene(s).