Uhlmann F, Nasmyth K
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030, Vienna, Austria.
Curr Biol. 1998 Oct 8;8(20):1095-101. doi: 10.1016/s0960-9822(98)70463-4.
Cohesion between sister chromatids, which opposes the splitting force exerted by the mitotic spindle during metaphase, is essential for their segregation to opposite poles of the cell during anaphase. In Saccharomyces cerevisiae, cohesion depends on a set of chromosomal proteins called cohesins, which include structural maintenance of chromosomes 1p (Smc1p), Smc3p and sister chromatid cohesion 1p (Scc1p). Strains with mutations in the genes encoding these proteins separate sister chromatids prematurely and fail to align them in metaphase. This leads to missegregation of chromosomes in the following anaphase.
In a normal cell cycle, Scc1p was synthesized and recruited to chromosomes at the onset of S phase. Using cells that expressed Scc1p exclusively from a galactose-inducible promoter, we showed that if Scc1p was synthesised only after completion of S phase, it still bound to chromosomes but failed to promote sister chromatid cohesion.
Cohesion between sister chromatids must be established during DNA replication, possibly following the passage of a replication fork. Furthermore, Scc1p (and other cohesins) are needed both for maintaining cohesion during mitosis and for establishing it during S phase. Establishment of sister chromatid cohesion is therefore an essential but hitherto neglected aspect of S phase.
姐妹染色单体之间的黏连在中期对抗有丝分裂纺锤体施加的分裂力，对于后期它们向细胞两极的分离至关重要。在酿酒酵母中，黏连依赖于一组称为黏连蛋白的染色体蛋白，其中包括染色体结构维持蛋白1p（Smc1p）、Smc3p和姐妹染色单体黏连蛋白1p（Scc1p）。编码这些蛋白的基因发生突变的菌株会过早分离姐妹染色单体，并且在中期无法使其排列整齐。这会导致后续后期染色体的错误分离。
在正常细胞周期中，Scc1p在S期开始时合成并募集到染色体上。利用仅从半乳糖诱导型启动子表达Scc1p的细胞，我们发现如果Scc1p仅在S期完成后合成，它仍会与染色体结合，但无法促进姐妹染色单体的黏连。
姐妹染色单体之间的黏连必须在DNA复制期间建立，可能是在复制叉通过之后。此外，Scc1p（和其他黏连蛋白）在有丝分裂期间维持黏连以及在S期建立黏连时都是必需的。因此，姐妹染色单体黏连的建立是S期一个重要但迄今被忽视的方面。
