Meiotic crossing-over is highly regulated such that each homolog pair typically receives at least one crossover (assurance) and adjacent crossovers are widely spaced (interference). Here we provide evidence that interference and assurance are mechanistically distinct processes that are separated by mutations in a new ZMM (Zip, Msh, Mer) protein from Saccharomyces cerevisiae, Spo16. Like other zmm mutants, spo16 cells have defects in both crossing-over and synaptonemal complex formation. Unlike in previously characterized zmm mutants, the residual crossovers in spo16 cells show interference comparable to that in the wild type. Spo16 interacts with a second ZMM protein, Spo22 (also known as Zip4), and spo22 mutants also show normal interference. Notably, assembly of the MutS homologs Msh4 and Msh5 on chromosomes occurs in both spo16 and spo22, but not in other zmm mutants. We suggest that crossover interference requires the normal assembly of recombination complexes containing Msh4 and Msh5 but does not require Spo16- and Spo22-dependent extension of synaptonemal complexes. In contrast, crossover assurance requires all ZMM proteins and full-length synaptonemal complexes.
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We thank N. Kleckner and members of the Shinohara laboratory for critical discussion, T. Tsubouchi and G.S. Roeder for sharing unpublished results, N. Kleckner (Harvard University) for providing zip1::LEU2 and D. Bishop (University Chicago) for materials used in this study. We are also indebted to A. Murakami, M. Kitamura, Y. Uegaki and A. Okabe for their technical assistance. This work was supported by a Grant-in-Aid from the Ministry of Education, Science, Sport and Culture to A.S. and M.S. and by US National Institutes of Health/National Institute of General Medical Sciences grant GM074223 to N.H.
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Shinohara, M., Oh, S., Hunter, N. et al. Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis. Nat Genet 40, 299–309 (2008). https://doi.org/10.1038/ng.83
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