Genetics, Vol. 164, 81-94, May 2003, Copyright © 2003

The Mus81/Mms4 Endonuclease Acts Independently of Double-Holliday Junction Resolution to Promote a Distinct Subset of Crossovers During Meiosis in Budding Yeast

Teresa de los Santosa, Neil Hunterb, Cindy Leea, Brittany Larkina, Josef Loidlc, and Nancy M. Hollingswortha
a Institute for Cell and Developmental Biology, Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794-5215,
b Center for Genetics and Development, Departments of Microbiology and Molecular and Cellular Biology, Division of Biological Sciences, University of California, Davis, California 95616-8665
c Cytology and Genetics, Institute of Botany, University of Vienna, A-1030, Vienna, Austria

Corresponding author: Nancy M. Hollingsworth, 314 Life Sciences Bldg., SUNY, Stony Brook, NY 11794-5215., nhollin{at}notes.cc.sunysb.edu (E-mail)

Communicating editor: A. P. MITCHELL

Current models for meiotic recombination require that crossovers derive from the resolution of a double-Holliday junction (dHJ) intermediate. In prokaryotes, enzymes responsible for HJ resolution are well characterized but the identification of a eukaryotic nuclear HJ resolvase has been elusive. Indirect evidence suggests that MUS81 from humans and fission yeast encodes a HJ resolvase. We provide three lines of evidence that Mus81/Mms4 is not the major meiotic HJ resolvase in S. cerevisiae: (1) MUS81/MMS4 is required to form only a distinct subset of crossovers; (2) rather than accumulating, dHJ intermediates are reduced in an mms4 mutant; and (3) expression of a bacterial HJ resolvase has no suppressive effect on mus81 meiotic phenotypes. Our analysis also reveals the existence of two distinct classes of crossovers in budding yeast. Class I is dependent upon MSH4/MSH5 and exhibits crossover interference, while class II is dependent upon MUS81/MMS4 and exhibits no interference. mms4 specifically reduces crossing over on small chromosomes, which are known to undergo less interference. The correlation between recombination rate and degree of interference to chromosome size may therefore be achieved by modulating the balance between class I/class II crossovers.




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