Function of Cohesin SMC1beta in Mammalian Meiosis

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In 2001 we reported the unexpected existence of a meiosis-specific SMC protein variant called SMC1ß, member of the SMC (Structural Maintenance of Chromosomes) protein family. SMC proteins are essential for chromosome condensation and sister chromatid cohesion, and are involved in DNA repair and recombination. All these processes are at the heart of meiosis, and have been specifically modified to serve the purpose of generating chromosomally normal germ cells. We recently obtained strong evidence that SMC1ß is required for meiotic sister chromatid cohesion, chromosome structure, and DNA recombination and thus for proper chromosome segregation during meiosis. We now aim at defining the molecular and cellular features of SMC1. In particular, we suggest that meiosisspecific expression of SMC1ß is regulated by specific promotor elements, and that the various functions of SMC1ß, and its specific chromosome association are determined through specific protein interactions. We aim at better understanding the biological role of SMC1ß itself, at exploring ist transcriptional regulation, at characterizing the complexes it forms, and will use approaches ranging from biochemical and molecular to cellular techniques and mouse models. Since it became clear from our recent studies that SMC1ß is a key protein in mammalian meiosis, our results will not only be important for understanding meiotic chromatin and DNA dynamics and meiosis-specific regulation of gene expression, but ¿ given the high incidence of aneuploidies in man ¿ also for insights into human reproductive biology and health.