Function of Cohesin SMC1beta in Mammalian Meiosis

在2001年，我们报告了一个意想不到的存在的减数分裂特异性SMC蛋白变异称为SMC 1 β，SMC（染色体结构维持）蛋白家族的成员。SMC蛋白是染色体凝聚和姐妹染色单体凝聚所必需的，并且参与DNA修复和重组。所有这些过程都是减数分裂的核心，并且已经被特别修改以用于产生染色体正常的生殖细胞。我们最近获得的强有力的证据表明，SMC150是需要减数分裂姐妹染色单体凝聚，染色体结构，DNA重组，从而为正确的染色体分离在减数分裂。我们现在的目标是定义SMC 1的分子和细胞特征。特别是，我们认为，减数分裂特异性表达的SMC110是由特定的启动子元件，SMC110的各种功能，其特定的染色体协会是通过特定的蛋白质相互作用。我们的目标是更好地了解SMC100本身的生物学作用，在探索它的转录调控，在表征它形成的复合物，并将使用从生物化学和分子到细胞技术和小鼠模型的方法。由于从我们最近的研究中可以清楚地看出，SMC 100是哺乳动物减数分裂中的一个关键蛋白，我们的研究结果不仅对于理解减数分裂染色质和DNA动力学以及基因表达的减数分裂特异性调控非常重要，而且考虑到人类非整倍体的高发病率，也有助于深入了解人类生殖生物学和健康。

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.