Meiotic Recombination

Abstract

Meiosis is the biological process in which diploid cells divide and reduce their chromosome number by half. During this process, homologous chromosomes must pair, synapse, and undergo recombination. A failure to successfully complete any one of these steps can lead to improper chromosome segregation and ultimately cellular aneuploidy. We are interested in understanding the molecular mechanisms that govern chromosome pairing, synapsis, and crossover formation. We are currently characterizing one mutant, me41, that was isolated in a screen for mutants that exhibited a high frequency of meiotic chromosome nondisjunction. Most embryos produced by me41 hermaphrodites are inviable, but a few progeny survive to adulthood, and a high percentage of these are male. Presumably, very few living embryos are produced because most embryos are aneuploid due to a severe reduction in meiotic crossing over. Consistent with this hypothesis, cytological analysis of me41 hermaphrodites reveals a high frequency of achiasmate chromosomes in oocyte nuclei. The severity of the me41 mutant phenotype is similar to the C. elegans spo-11 null mutant phenotype. The spo-11 null mutant lacks the enzyme required for generating the double strand DNA breaks (DSBs) that initiate meiotic recombination (see Dernburg, et al.). Since radiation induced breaks can substitute for the double strand breaks normally produced by SPO-11, we are testing whether or not radiation can also rescue the me41 mutant phenotype. Preliminary studies indicate that me41 cannot be rescued by gamma irradiation, suggesting that the wild-type gene product functions sometime after the double strand break initiation step and/or performs multiple functions. The me41 mutation has been mapped to a roughly 1 Mb region of chromosome V between unc-42 and STS marker bP1. A search of the predicted open reading frames in this region reveals that one of the ORFs is similar to the Saccharomyces cerevisiae gene MRE11, which is involved in both generation and processing of double strand breaks during meiosis and in double strand break repair during vegetative growth. We are currently testing whether or not me41 is a mutation in the predicted C. elegans mre-11 gene.