The laboratory is focused on mechanisms that maintain genome stability in Saccharomyces cerevisiae. Specific areas of research include:
1. Mechanisms of chromosome segregation during meiosis:
a) Mechanisms of chromosome segregation during meiosis: Crossovers establish physical connections between homologs and ensure their accurate segregation. In S. cerevisiae and mammals, meiotic crossing over is controlled by a subset of the mismatch repair related factors MSH4-MSH5 and MLH1-MLH3. We make use of a sensitized system of msh4, msh5 hypomorphs (Figure 1) that can segregate chromosomes in S. cerevisiae with up to a two fold reduction in crossovers to ask: how are crossover number and placement on homolog pairs optimized to assure disjunction? What mechanisms maintain crossover assurance on all homolog pairs? High resolution, genome wide crossover maps are used to address these questions (Figure 2). We also perform genetic screens to characterize mutations that disrupt crossover assurance in S. cerevisiae
2. Meiotic recombination and mutation load:
Mutations can be deleterious and produce genetic diseases in organisms but are also the raw material for evolution of the population. Sexual (meiotic) populations can remove deleterious mutations by meiotic recombination and mating and thereby have fitness advantage over mitoticaly reproducing populations . Population genetic analysis in humans, drosophila and other model organisms have shown that genomic regions that have low recombination rates experience a higher load of deleterious mutations. We use meiotic mutants that have altered recombination levels to experimentally determine how they affect a fixed mutational load.
Related references
Nishant KT* , Chen C, Shinohara M, Shinohara A, Alani E (2010) Genetic Analysis of Bakers Yeast Msh4-Msh5 Reveals a Threshold Crossover Level for Meiotic Viability, PLOS GENETICS, 6(8): e1001083. doi:10.1371/journal.pgen.1001083 [PDF File] [Link to paper at publisher's site]
Nishant KT*, Wei, W*., Mancera, E*., Argueso, L., Schlattl, A., Delhomme, N., Ma, X., Bustamante, C., Korbel, J., Gu, Z., Steinmetz, M. and Alani, E. (2010) The baker’s yeast diploid genome is remarkably stable in vegetative growth and meiosis. PLoS Genetics 6:e1001109. [PDF File] [Link to paper at publisher's site]