Mechanisms and Regulation of Telomere-Led Chromosome Movements in Yeast and Mouse

LEE, E;; BISIG CG; PREVIATO DE ALAMELDA, L,; DITAMO Y; CONRAD, M; DRESSER, ME; PEZZA, RJ

New London, NH, US

Conferencia; 14th Meiosis Gordon Research Conference Molecular Mechanisms and Regulation of Meiosis Across Species; 2018

Gordon Research Conference

Chromosome segregation errors occur in ~10%-30% of human meiocytes, resulting in aneuploid gametes. This is the leading cause of spontaneous abortions and aneuploid-based birth defects in humans. Some examples of human hereditary diseases caused by aneuploidies are Down, Klinefelter, Edwards and Turner syndromes. Proper segregation of chromosomes during meiosis requires the maternal and paternal homologous chromosomes to pair and synapse. Telomere-led rapid movements (RPMs) observed at prophase of meiotic dividing cells are required to promote proper chromosome pairing and synapsis. RPMs have been observed in many species; however, the mechanism that generates them and their regulation are still not completely understood. We have previously shown that microtubules and the protein complex SUN1/KASH5 (LINC) promote RPMs in mouse spermatocytes. More recently we demonstrated that molecular motors from the Kinesin family participate in the generation of RPMs by creating a connection between the LINC complex and cytoskeleton microtubules. In this project, we propose to study the influence of post-translational modifications of tubulin and microtubules on the mechanisms that generate the RPMs in mice spermatocytes. We will use biochemical and cell biology approaches to characterize microtubule modifications. Three-dimensional time-lapse microscopy will allow us to visualize and quantify RPMs in spermatocytes treated with tubulin modifier inhibitors. Overall, results from this project will reveal the mechanisms that direct RPMs during meiosis in mammals, which have direct implications in the correct segregation of meiotic chromosomes and avoidance of aneuploid gamete formation.