Function of Cohesin SMC1beta in Mammalian Meiosis

2001年，我们报道了一种减数分裂特异的SMC蛋白变体，称为SMc1？，它是SMC(染色体结构维护)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，并参与DNA修复和重组。所有这些过程都是减数分裂的核心，并经过专门的修改，以产生染色体正常的生殖细胞。我们最近获得了强有力的证据，表明SMc1？是减数分裂姐妹染色单体凝聚力、染色体结构和DNA重组所必需的，从而是减数分裂过程中染色体正确分离所必需的。我们现在的目标是定义SMC1的分子和细胞特征。特别地，我们认为SMc1？的减数分裂特异性表达受特定启动子元件的调控，SMc1？的各种功能及其特定的染色体结合是通过特定的蛋白质相互作用来决定的。我们的目标是更好地了解SMC1？本身的生物学作用，探索转录调控，确定其形成的复合体的特征，并将使用从生化和分子到细胞技术和小鼠模型的各种方法。由于我们最近的研究表明SMc1？是哺乳动物减数分裂中的关键蛋白质，我们的结果不仅对于理解减数分裂染色质和DNA动力学以及减数分裂特有的基因表达调控具有重要意义，而且考虑到人类非整倍体的高发生率，也有助于深入了解人类的生殖生物学和健康。

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.