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Roles For Telomere-Led Chromosome Motion And Crossover Resolution During Meiosis In Saccharomyces Cerevisiae
During meiosis, multiple mechanisms act to promote accurate segregation of chromosomes, ensuring that all progeny receive exactly one copy of each chromosome. To achieve this during meiosis, chromosomes need to pair, recombine, and correctly attach to the meiotic spindle. The focus of my thesis is to understand early events in meiosis that promote chromosome segregation, including telomere-led chromosome movements and crossover placement and regulation. Telomere-led chromosome movements are a conserved feature of Meiosis I. Various roles have been proposed for such chromosome motions, including promoting homolog pairing and removing inappropriate chromosomal interactions. Using a "one-dot/two-dot tetR-GFP" assay in budding yeast, I found that csm4[INCREMENT] strains, which are defective in telomere-led chromosome movements and proper Meiosis I disjunction, are also defective in homolog pairing. I then performed a systematic mutational analysis of CSM4. This screen yielded one allele, csm4-3, that conferred a null-like meiotic delay but had near wild-type levels of spore viability. Interestingly, compared to wild-type, csm4-3 conferred an intermediate phenotype in homolog pairing, but reduced average chromosome velocity. Furthermore, I found that the meiotic delay was essential for spore viability and Meiosis I disjunction in csm4-3. Based on these observations, I propose that occasional and rapid chromosome movements over an extended period of time are sufficient to promote wild-type levels of recombination and high spore viability; however, sustained and rapid chromosome movements are required to promote efficient meiotic progression. Crossover regulation is also important in promoting disjunction of homologs in Meiosis I, and is regulated through an interference-dependent mechanism involving Msh4-Msh5 and Mlh1Mlh3. Crossover interference helps ensure that each homolog pair receives an obligate crossover, facilitating proper disjunction in the first meiotic division. Previously, the Alani laboratory detected a crossover threshold in msh4/5 mutants where meiotic crossover levels could be decreased up to two-fold without lowering spore viability. I show that a set of mlh3 ATPase mutants do not confer a crossover threshold pattern; instead, a linear relationship was observed between spore viability and meiotic crossing over. These data are consistent with Mlh1-Mlh3 acting after obligate crossover decisions have been made. iv
meiosis; crossing over; Csm4; Mlh3; telomere-led chromosome motion
Wolfner, Mariana Federica; Schimenti, John C.
Ph.D. of Biochemistry
Doctor of Philosophy
dissertation or thesis