FUNCTIONS OF THE YEAST MEIOTIC RECOMBINATION GENES, MRE11 AND MRE2

Recombination allows separation of favorable and unfavorable mutations in an old linkage. It provides a means of spreading for a favorable allele and of eliminating an unfavorable allele in a species. Recombination must, therefore, have played a crucial role in evolution of the genome. Furthermore, recombination is also part of various biological functions in a cell. It is involved in repair of DNA damage (1), a primer formation in T4 DNA replication (2), production of a variety of immunoglobulin genes and T-cell receptor genes (3), switching on or off the alternative gene expressions by DNA inversion or gene conversion of a particular region of a chromosome (4, 5), and chromosome disjunction in meiosis I (6). The study of recombination is important for the understanding of basic biological processes. Molecular mechanisms of recombination have been studied extensively using prokaryotes and have revealed the important roles of RecA protein of Escherichia coli (7, 8); recent findings extended the generality of these results to eukaryotes. Several recA gene homologues in eukaryotes including human and mouse were cloned (9, 10). They are structurally and functionally similar to those of the RecA protein (11, 12). These findings provide us a promising clue to elucidation of the mechanisms of recombination in eukaryotes. Genetic recombination occurs at the highest frequency in meiosis in eukaryotes. In yeast, the frequency is about 1,000 times higher than that in mitosis (23). The high recombination frequency requires formation of synaptonemal complexes (SC), which are an ordered structure of paired homologous chromosomes (13). The formation of synaptonemal complexes and the initiation of the recombination occur through formation of double-strand breaks (DSBs) at meiosis-specific recombination hot-spots (13). This makes knowledge of the mechanism of formation of DSBs valuable to our understanding of the molecular mechanism of the recombination. We approached this problem by isolating mutants that affect the initiation of meiotic recombination. In this review we will report the identification of two new genes, MRE11 and MRE2 that are involved in formation of DSBs.