In meiosis, chromosomes replicate once, then undergo two rounds of segregation to generate haploid meiotic products. The aberrant segregation of chromosome during meiosis generates products that are aneuploid have an incorrect number of chromosomes). In humans, meiotic aneuploidy is the leading cause of pregnancy loss, congenital birth defects, and mental retardation. Exposure to environmental agents (pollutants, pesticides hormone mimetics, etc.) is implicated as a risk factor. However, it is difficult to gauge significant effects in humans and there are no good models for large-scale screening. The goal of our work is to develop and validate a system for high-through put screening (HTS) of chemical libraries to identify those that cause meiotic aneuploidy (meiotic aneugenes). The system is based on the unique biology of the fission yeast Schizosaccharomyces pombe, in which meiosis can be induced in a synchronous fashion and in which meiotic chromosome mis-segregation can be monitored directly. Selectable markers will be configured to allow quantitative analysis of the frequency of meiotic aneuploidy following exposure to chemical agents. Additional features will be incorporated into the system for secondary screening and to permit identification of specific molecular mechanisms by which any given chemical affects meiosis. The system will be validated and calibrated by using mutants that affect meiotic sister chromatid cohesion and meiotic recombination and by testing chemicals known to cause meiotic errors. Upon validation, the systems will be made available to a molecular libraries screening center network site for HTS screening of potential meiotic aneugens.

Sharif, W.D., G.G. Glick, M.K. Davidson, and W.P. Wahls. (2002). Distinct functions of S. pombe Rec12 (Spo11) protein and Rec12-dependent crossover recombination (chiasmata) in meiosis I; and a requirement for Rec12 in meiosis II. Cell Chromo. 1, 1-14.

Davidson, M.K., H.K. Shandilya, W.D. Sharif, and W.P. Wahls (2003). Atf1oPcr1oM26 complex and nucleosome remodeling promote double-strand DNA break-induced meiotic recombination. Rec. Res. Dev. Mol. Cell. Biol. 4, 189-208. [invited review / book chapter]

Sharif, W.D., M.K. Davidson, and W.P. Wahls (2003). Rec12 (Spo11) recombinase of fission yeast promotes a backup, distributive pathway for chromosome segregation in meiosis I. J. Ark. Acad. Sci. 57, 147-155.

Wu, H., J. Gao, W.D. Sharif, M.K. Davidson, and W.P. Wahls (2004). Purification, folding, and characterization of Rec12 (Spo11) meiotic recombinase of fission yeast. Protein Expr. Purif. 38, 136-144.

Davidson, M.K., N.P. Young, G.G. Glick, and W.P. Wahls (2004). Meiotic chromosome segregation mutants identified by insertional mutagenesis of Schizosaccharomyces pombe; tandem-repeat, single-site integrations. Nucleic Acids Res., 32, 4400-4410.

Davidson, M.K., H.K. Shandilya, K. Hirota, K. Ohta, and W.P. Wahls (2004). Atf1-Pcr1-M26 complex directly links stress-activated MAPK and PKA pathways via chromatin remodeling of cgs2+. J. Biol. Chem. 279, 50857-50863.

DeWall, K.M., M.K. Davidson, W.D. Sharif, C.A. Wiley, and W.P. Wahls (2005). A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202; and persistence of Rec12 protein after completion of recombination. Gene, 356, 77-84

Wahls, W.P., K.M. DeWall, and M.K. Davidson (2005). Mapping of ssDNA nicks within dsDNA genomes by two-dimensional gel electrophoresis. J. Ark. Acad. Sci. 59:178-186.