The Mnd1 Protein Forms a Complex with Hop2 To Promote Homologous Chromosome Pairing and Meiotic Double-Strand Break Repair

Abstract

The hop2 mutant of Saccharomyces cerevisiae arrests in meiosis with extensive synaptonemal complex (SC) formation between nonhomologous chromosomes. A screen for multicopy suppressors of a hop2-ts allele identified the MND1 gene. The mnd1-null mutant arrests in meiotic prophase, with most double-strand breaks (DSBs) unrepaired. A low level of mature recombinants is produced, and the Rad51 protein accumulates at numerous foci along chromosomes. SC formation is incomplete, and homolog pairing is severely reduced. The Mnd1 protein localizes to chromatin throughout meiotic prophase, and this localization requires Hop2. Unlike recombination enzymes such as Rad51, Mnd1 localizes to chromosomes even in mutants that fail to initiate meiotic recombination. The Hop2 and Mnd1 proteins coimmunoprecipitate from meiotic cell extracts. These results suggest that Hop2 and Mnd1 work as a complex to promote meiotic chromosome pairing and DSB repair. The identification of Hop2 and Mnd1 homologs in other organisms suggests that the function of this complex is conserved among eukaryotes.

We thank Douglas Bishop and Akira Shinohara for anti-Rad51 antibodies. We are grateful to Jennifer Fung, Erica Hong, Jun-Yi Leu, and Beth Rockmill for comments on the manuscript and to Tomomi Tsubouchi for helpful discussions. The Howard Hughes Biopolymer/Keck Foundation Biotechnology Resource Laboratory at Yale University synthesized oligonucleotides and performed DNA sequencing analysis.

This work was supported by the Howard Hughes Medical Institute and by a Postdoctoral Fellowship for Research Abroad granted to H.T. by the Japan Society for the Promotion of Science.