genetic and molecular analysis of meiosis in yeast
	Shirleen Roeder, Ph.D. Professor Emeritus of Molecular, Cellular & Developmental Biology and Eugene Higgins Professor of Genetics; Investigator, HHMI Email: shirleen.roeder@yale.edu Web site B.S. Dalhousie University 1973; Ph.D. University of Toronto 1978

Meiosis is a special type of cell division that produces haploid gametes from diploid parental cells. During the first division of meiosis, homologous chromosomes pair with each other, undergo genetic recombination, and then segregate to opposite poles. Homolog pairing culminates in formation of the synaptonemal complex, which consists of two lateral elements separated by a central region. Each lateral element corresponds to the protein backbone of one pair of sister chromatids.

To investigate meiotic chromosome behavior, we have isolated and characterized yeast mutants defective in structural components of the synaptonemal complex. The Zip1 protein is a building block of the central region, while Red1 is a component of lateral elements. Zip2 is present at sites of synaptic initiation, where it promotes Zip1 assembly. Using the zip1, red1 and zip2 mutants as tools, we are exploring the function and assembly of the synaptonemal complex. All three mutants undergo significant levels of recombination, demonstrating that synapsis is not necessary for meiotic genetic exchange. The Zip2 protein colocalizes with proteins directly involved in double-strand break repair, indicating that synapsis initiates at the sites of genetic recombination events. Studies of Red1 indicate that this protein is required to establish cohesion between sister chromatids during meiosis. Meiotic sister-chromatid cohesion also requires the meiosis-specific protein kinase, Mek1, which associates with and phosphorylates the Red1 protein. Chromosome synapsis is preceded by an homology search that aligns chromosomes at a distance. A circular chromosome pairs poorly with its homolog, suggesting a role for telomeres in chromosome pairing. This pairing requires the meiosis-specific Ndj1 protein, which localizes to telomeres. The hop2 mutant undergoes synapsis between nonhomologous chromosomes, indicating that Hop2 also participates in pairing.

Several meiotic mutants (including zip1 and zip2) arrest in meiotic prophase due to a checkpoint triggered by defects in recombination and synapsis. Identification of mutants defective in meiotic checkpoint function demon-strates that arrest at pachytene is due to inhibitory phosphorylation of the cyclin-dependent protein kinase, Cdc28. This modification is carried out by the Swe1 protein kinase, which increases in abundance and is phosphorylated when the checkpoint is triggered. In addition, chromatin silencing factors play a role in the control of meiotic cell cycle progression. Cell cycle arrest requires Sir2, and the meiosis-specific protein, Pch2, both of which repress meiotic recombination within the tandem array of ribosomal RNA genes.

Selected Publications

Leu, J.-Y., P.R. Chua and G.S. Roeder (1998) The meiosis-specific Hop2 protein of S. cerevisiae ensures synapsis between homologous chromosomes. Cell, 94:375-386.

Bailis, J.M. and G.S. Roeder. (1998) Synaptonemal complex morphogenesis and sister-chromatid cohesion require Mek1-dependent phosphorylation of a meiotic chromosomal protein. Genes Dev., 12:3551-3563.

San-Segundo, P.A. and G.S. Roeder. (1999) Pch2 links chromatin silencing to meiotic checkpoint control. Cell, 97:313-324

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