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Genetics, Vol. 168, 35-48, September 2004, Copyright © 2004
doi:10.1534/genetics.104.027789
Does Crossover Interference Count in Saccharomyces cerevisiae?
Franklin W. Stahl*,1,
Henriette M. Foss*,
Lisa S. Young*,
Rhona H. Borts
,
M. F. F. Abdullah
and
Gregory P. Copenhaver
* Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229
Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom
Department of Microbiology, Mara University of Technology, 40450 Shah Alam, Malaysia
Department of Biology and The Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599
1 Corresponding author: Institute of Molecular Biology, 1370 Franklin Blvd., 1229 University of Oregon, Eugene, OR 97403-1229.
E-mail: fstahl{at}molbio.uoregon.edu
We previously proposed a "counting model" for meiotic crossover interference, in which double-strand breaks occur independently and a fixed number of noncrossovers occur between neighboring crossovers. Whereas in some organisms (group I) this simple model alone describes the crossover distribution, in other organisms (group II) an additional assumptionthat some crossovers lack interferenceimproves the fit. Other differences exist between the groups: Group II needs double-strand breaks and some repair functions to achieve synapsis, while repair in group I generally occurs after synapsis is achieved; group II, but not group I, has recombination proteins Dmc1, Mnd1, and Hop2. Here we report experiments in msh4 mutants that are designed to test predictions of the revised model in a group II organism. Further, we interpret these experiments, the above-mentioned differences between group I and II meiosis, and other data to yield the following proposal: Group II organisms use the repair of leptotene breaks to promote synapsis by generating double-Holliday-junction intermediates that lock homologs together (pairing pathway). The possible crossover or noncrossover resolution products of these structures lack interference. In contrast, for both group I and group II, repair during pachytene (disjunction pathway) is associated with interference and generates only two resolution types, whose structures suggest that the Holliday junctions of the repair intermediates are unligated. A crossover arises when such an intermediate is stabilized by a protein that prevents its default resolution to a noncrossover. The protein-binding pattern required for interference depends on clustering of sites that have received, or are normally about to receive, meiotic double-strand breaks.
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