Abstract: Mutants defective in meiotic recombination were isolated using a disomic haploid strain of S. cerevisiae, and were classified into 11 genes. Two, MRE2 and MRE11, are new genes and nine are previously identified genes. The mre2 and mre11 deletion mutants are proficient in mitotic recombination, but are defective in meiotic recombination and in formation of viable spores. The spore inviability, however, is alleviated by an additional mutation, spo13, which bypasses meiosis I. In addition, neither meiosis specific DSBs at recombination hot-spots nor formation of synaptonemal complex occur in either mutant. Therefore, these two genes are involved in the formation of DSBs in meiotic recombination. While a temperature sensitive mre11-1 mutant is able to form DSBs at a permissive temperature, the formed DSBs are unable to resect at non permissive temperature. Therefore, the MRE11 gene is also involved in some step of the repair process after the DSB formation. Analysis of properties of the mre11 disruption mutant as well as the xrs2 mutant showed a similarity to those of the rad50 disruptant. We found that the mre11 disruption mutation is epistatic to rad50S mutation, as the xrs2 deletion mutation is epistatic to rad50S with regard to DSBs. Therefore, these three genes form an epistatic group. Interaction of the Mre11 protein with the Rad50 and the Xrs2 protein as well as alone was shown in vivo using the two-hybrid system. The MRE2 gene encodes a protein containing two sets of RRM. Deficiency of recombination in a mre2 mutant that has an amino acid substitution in the N-terminal RRM can be suppressed by the MER2 gene on the multicopy plasmid. Further analysis showed that the Mre2 protein is involved in meiosis-specific splicing of the MER2 transcripts in cooperation with the Mer1 protein. In conclusion, MRE genes are involved in the initiation of meiotic recombination through the formation of DSBs at recombination hot-spots in S. cerevisiae.