Molecular requirements for nuclear envelope attachment and movements of meiotic telomeres

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Accurate separation of maternal and paternal chromosomes during the first division of meiosis requires pairing, synapsis and recombination between the homologs. A very central aspect in preparing homologs for separation is the directed movement of telomeres that culminates in bouquet-formation, which in turn is crucial for faithful homolog assortment and hence essential for genome haploidization. This kind of telomere driven chromosome gathering is a widespread phenomenon that applies for almost every sexually reproducing eukaryote. However, up to the present the molecular mechanisms required for telomere attachment to the nuclear envelope and their directed movements are poorly understood. To learn about this vitally important issue we for some time past are engaged with the identification as well as molecular and functional characterization of protein components involved in these processes. Within the proposed project we would like to follow up our recent successful investigations by which we could significantly contribute to our current knowledge in terms of how telomeres attach to the nuclear envelope. Our current interest lies in elucidating the role of the nuclear envelope and its components (particularly of meiotic lamin C2, SUN-domain proteins, as well as yet unknown binding partners) in telomere attachment and movements. We will carry out a variety of different approaches, including the detailed analysis of our recently generated lamin C2 ‘knockout’ mouse as well as the analysis of further knockout models with respect to potential effects on meiotic telomere behaviour. Furthermore, we will hunt for yet unknown proteins required for telomere attachment and/or movement. Recently, we have isolated two promising candidates that now should be characterized in detail.