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.