Murray, Andrew WLumbroso, Gal2023-06-0220232023-05-032023-05Lumbroso, Gal. 2023. The role of the B-type cyclin Clb4 in budding yeast meiosis. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.30487528https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37375570Meiosis is a specialized cell division that includes a round of DNA replication, followed by two rounds of chromosome segregation, producing cells with half the ploidy of the original cell (gametes). The second meiotic division, meiosis II, segregate sister chromatids. The first division, meiosis I, segregates homologous chromosomes (homologs), a process that requires recombination between each homolog pair. Errors in meiosis I chromosome segregation are a frequent source of aneuploidy and reduced gamete viability. In the budding yeast Saccharomyces cerevisiae, diploid cells that commit to meiosis produce four haploid gametes (a tetrad) enveloped in a resilient ascus. We selected for mutations that enable gamete viability in the absence of recombination. Loss-of-function mutations in the B-type cyclin CLB4 arose during that selection. This led us to find that in at least two strains of S. cerevisiae, Clb4 prevents the premature separation of sister chromatids in meiosis I. We show that meiosis in CLB4 deletion mutants from the SK1 and Y55 strain backgrounds often terminates after a single division, in which sister chromatids are segregated instead of homologous chromosomes, demonstrating a novel role of Clb4 in establishing the meiosis I chromosome dynamics and promoting meiotic progression. We reconfirm that in contrast to Y55 and SK1, meiotic progression is largely unperturbed in CLB4 deletion mutants from the W303 strain background, and attempt to explain the genetic basis of this phenotypic difference.application/pdfenBudding yeastCLB4CyclinMeiosisSaccharomyces cerevisiaeSPO11BiologyThesis or Dissertation2023-06-020009-0000-9259-953X