Nancy M. Hollingsworth

Ph.D University of Washington 1988

Meiotic chromosome synapsis, recombination and segregation in yeast

My lab is interested in how homologous chromosomes are able to pair, recombine and segregate properly during meiosis. This is a fundamental problem in biology for all sexually reproducing organisms. Chromosome synapsis, recombination and segregation must all occur properly during meiosis in order to generate chromosomally balanced gametes. For example, in humans, failure of any of these events leads to spontaneous abortions and in some cases to severe birth defects such as Trisomy 21 or Down's syndrome.Meiosis is a highly conserved process throughout evolution. Therefore I am studying meiosis in the model yeast system, Saccharomyces cerevisise where genetic, cytological and biochemical approaches are feasible. My focus is on identifying genes that promote segregation of homologous chromosomes by facilitating the formation of crossovers. These genes fall into two classes: 1) those which encode structural or regulatory components of the synaptonemal complex (SC), the protein structure formed when homologous chromosomes pair during meiotic prophase. The second class include genes that encode proteins which directly facilitate interhomolog reciprocal recombination.Using a genetic screen, I have indentified and characterized genes of both classes, HOP1 and MSH5. HOP1 encodes a structural component of the SC. The current focus of my lab is on the meiosis-specific MutS homolog, MSH5. MutS homologs are present in a wide variety of species, from bacteria to man, and are important in the process of repairing mismatched DNA basepairs which occur as a result of recombination or errors in DNA replication. Unlike the other MutS homologs, MSH5 has no role in mismatch repair; instead MSH5 acts specifically during meiosis to promote crossing over, presumably by directly binding a recombination intermediate. By understanding how these proteins function during meiosis, a clearer picture of proper chromosome segregation will be obtained.

  • Hollingsworth, N. M. and B. Byers (1989). HOP1: a yeast meiotic pairing gene. Genetics 121: 445-462.
  • Hollingsworth, N. M., L. Goetsch and B. Byers (1990) The HOP1 gene encodes a meiosis-specific component of yeast chromosomes. Cell 61: 73-84.
  • Vershon, A. K., N. M. Hollingsworth and A. D. Johnson (1992) Meiotic induction of the yeast HOP1 gene is controlled by positive and negative regulatory elements. Mol. Cell. Biol. 12: 3706-3714.
  • Hollingsworth, N. M. and A. D. Johnson (1993) A conditional allele of the yeast HOP1 gene is suppressed by overexpression of two other meiosis-specific genes: RED1 and REC104. Genetics 133: 785-797.
  • Friedman, D.B., N. M. Hollingsworth and B. Byers (1994) Insertional mutations in the yeast HOP1 gene: Evidence for Multimeric Assembly in Meiosis. Genetics 136: 449-464.
  • Hollingsworth, N. M., L. Ponte and C. Halsey (1995). MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes and Dev. 9: 1728-1739.