Cloning and characterization of a novel meiotic pairing gene in Caenorhabditis elegans, and a search for genes with related functions

Research project P 14642 Meiotic pairing genes in C. elegans Josef LOIDL 09.10.2000 Meiosis is a specialized cell division that leads to the reduction of the diploid chromosome complement and results in the production of haploid gametes. Compared to the mitotic division, the first meiotic division is unique as homologous parental chromosomes associate with each other to enable the reciprocal exchange of corresponding portions and the orderly disjunction of chromosomes. Our current understanding of the mechanisms leading to meiotic chromosome pairing is still limited, and stems mostly from classical cytological observations and from results obtained via genetical studies in budding yeast. However, there is some evidence that some aspects of meiosis may differ between yeast and multicellular eukaryotes with more complex genornes. To better understand chromosome pairing we propose to pursue a genetic approach using C. elegans as model system. In accordance with the situation in mammals (but not in yeasts) we have shown that in C. elegans defects in chromosome pairing and recombination lead to the activation of a checkpoint that results in the elimination of affected cells by programmed cell death. Taking advantage of that knowledge we isolated a novel mutant (tentatively called rid- 11) that leads to excessive apoptosis due to a failure in meiotic chromosome pairing. In this project we want to clone the RID- 11 gene and to further characterize its precise role in meiotic pairing. Furthermore, we will use our finding that meiotic defects lead to ex-cessive apoptosis (a phenotype that can be easily detected in C. elegans) to screen for additional mutants defective in meiotic chromosome pairing and recombination.

Meiosis is a specialized cell division that leads to the reduction of the diploid chromosome complement and results in the production of haploid gametes. During meiosis, pairs of homologous chromosomes (one from each parent) separate in a first round (Meiosis I) and each chromosome splits in its two sister chromatids during a second round (Meiosis II). Before homologous chromosomes separate at meiosis I, they pair and exchange corresponding portions (recombination). In this project we studied chromosome pairing and recombination in the meiosis of the nematode Caenorhabditis elegans by mutant screens and reverse genetic approaches. Several meiotic genes were identified and characterized. One of them (zhp-3) is a homologue of ZIP3, a yeast gene with a function in the initiation of stable chromosome pairing. In C. elegans this gene has assumed a different role, since it is not required for pairing. The product of another gene, scc-3, was found to be important both for the pairing and the separation of homologous chromosomes in meiosis. Work on mfp-1, a gene with a putative role in the recognition of homology, being a condition for chromosome pairing, is still in progress. Altogether, the uncovering of the functions of some of the large number of meiotic genes has led to a better understanding of the meiotic process.