Functions of cohesin SMC1Beta in mammalian meiotic chromosome structure and dynam

姐妹染色单体内聚和dna的结合是减数分裂的核心，减数分裂是细胞发育的关键过程

Sister chromatid cohesion and DNArecombination are at the heart of meiosis, which is a key process for gametogenesis. Maintenance ofgenome integrity during gametogenesis is of utmost medical importance, considering the extraordinarily high incidence of aneuploidies in man. Meiotic chromatin dynamics is specifically distinct from mitotic, and is far from being understood. In this application for renewal, we ask for continuous support of our studies on a meiosis-specific cohesin protein, SMCi[3, that we have isolated and initially characterized during the first grant period. SMClp turned out to be a central element of meiotic chromosome behavior. As we showed, SMCifJ is required for sister chromatid cohesion of meiotic chromosomes, for meiosis-specific telomere movements, and for proper meiotic DNA recombination. Molecular, cellular and organismal studies are now needed to decipher the mechanisms through which SMCip works, to put its function into the larger context of meiotic chromosome structure and behavior, and to further elucidate its biological role. Our central hypothesis suggests that SMCi(3 plays a specific and essential role in determining meiotic chromosome structure and dynamics and thus in avoiding aneuploidies. In particular, we propose that SMClp, within specific complexes, contributes to synaptonemal complex formation and the organization of axis and chromatin loops. We also predict that SMClp plays a direct role in telomere function. We further suggest that turnover of the SMCi(3 cohesin complexis key to maintenance of sister chromatid cohesion during female meiosis, specifically dictyate arrest, and thus important to avoid aneuploidies. Our aim is to determine the role of SMClp during dictyate arrest and in the age-related increase in aneuploidies. In addition we propose that SMCi|3 fulfills distinct functions from the ubiquitous SMCicx. Our aim is to test these hypotheses. Since the available evidence suggests SMCip to be a key protein in mammalian meiosis, our results will be important not only for a better understanding of mammalianSMC protein biology, but also for understanding of meiosis-specificfeatures of chromosome structure, and thus for human reproductive biology and health with particular significance for prevention of aneuploidy. Proper chromosome structure and segregation are essential for meiosis, i.e.gametogenesis. The identification and characterization of proteins required for these processes, such as cohesins, is of paramount importance not only for basic biology, but even more so for human health, since man suffers from an extraordinarilyhigh rates of chromosomal abnormalities that emerge during gametogenesis and cause, for example, Down syndrome.