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Faithful chromosome segregation in C. elegans meiosis

 

Principal Investigator: Verena Jantsch

Meiosis is the specialized cell division that generates haploid germ cells, a requirement to compensate for doubling of the chromosomal content after fertilization. Meiosis also ensures genetic diversity by recombination. Defects in this process lead to unfaithful chromosome segregation and are a major cause for miscarriages and birth defects. For successful recombination in meiotic prophase, homologous chromosomes have to recognize each other, pair, and finally closely associate, mediated by the synaptonemal complex, a well conserved, tripartite proteinacious structure. Interestingly, few genes and factors involved in the meiotic pairing process have been identified today. Research in my lab is therefore directed towards the identification of genes and processes essential in meiotic prophase. Special emphasis is given the study of the mechanisms of recognition and pairing of homologous chromosomes.

Excellent forward and reverse genetics and easy cytological observation of all meiotic stages make the nematode Caenorhabditis elegans an excellent model system for our studies. In forward genetic screens we have isolated numerous novel meiotic mutants that provide(d) us insight into prophase I events.

In meiotic prophase I chromosomes are moved by cytoplasmic forces transferred to the nucleus via the SUN/KASH protein module (components of the outer and inner nuclear envelope that connect chromosomes to cytoplasmatic microtubules). Abrogation of chromosome movement, as we demonstrated with the sun-1(jf18) allele, leads to precocious synapsis involving non-homologous chromosomes. We study the nature of chromosome movement and its regulation. Concomitant with chromosome movement when the SUN-1 protein redistributes into aggregates at chromosome ends, the inner nuclear envelope protein SUN-1 is reversibly modified by multiple kinases. We try to understand the contribution of the modifications to faithful chromosome segregation.

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