Wang Xiaoxing, Dai Wei
Division of Molecular Carcinogenesis, Department of Medicine, New York Medical College, Basic Science Building, Room A22, Valhalla, NY 10595, USA.
Exp Cell Res. 2005 Oct 15;310(1):1-9. doi: 10.1016/j.yexcr.2005.07.018.
To ensure sister chromatids to be equally transmitted to daughter cells, it is imperative that physical association of sister chromatids is maintained during S, G2, and early mitosis until the onset of anaphase. Cohesion of sister chromatids in eukaryotes is largely achieved by the cohesin complex. In vertebrates, cohesin molecules are dissociated from chromosome arms but not from centromeres during prophase by the so-called prophase pathway. Although it remains unclear what is the molecular basis by which centromeric cohesin is retained, a flurry of recent studies have shed light on a family of proteins named Shugoshin (Sgo) that are evolutionarily conserved across eukaryotes. Sgo1 functions as a protector of centromeric cohesin during meiosis in yeast and during mitosis in high eukaryotes. Suppression of Sgo1 function results in premature separation of sister chromatids in both meiosis and mitosis. The discovery of members of the Sgo family may help to explain how centromeric cohesin is protected from dissociation from DNA until the onset of anaphase. Given the importance of chromosome cohesion in the maintenance of genomic stability, further characterization of Sgo1 and related molecules may also open up new avenues of research for developing new strategies for cancer intervention.
为确保姐妹染色单体能够均等地传递给子细胞，在S期、G2期以及有丝分裂早期直至后期开始之前，维持姐妹染色单体的物理连接至关重要。真核生物中姐妹染色单体的黏连主要通过黏连蛋白复合体实现。在脊椎动物中，在前期，黏连蛋白分子通过所谓的前期途径从染色体臂上解离，但不从着丝粒上解离。尽管尚不清楚着丝粒黏连蛋白得以保留的分子基础是什么，但最近一系列研究揭示了一类名为守护蛋白（Sgo）的蛋白质家族，这类蛋白在真核生物中具有进化保守性。Sgo1在酵母减数分裂期间以及高等真核生物有丝分裂期间作为着丝粒黏连蛋白的保护因子发挥作用。抑制Sgo1的功能会导致减数分裂和有丝分裂中姐妹染色单体过早分离。Sgo家族成员的发现可能有助于解释着丝粒黏连蛋白如何在后期开始之前一直受到保护而不与DNA解离。鉴于染色体黏连在维持基因组稳定性中的重要性，对Sgo1及相关分子的进一步表征也可能为开发癌症干预新策略开辟新的研究途径。
