Bernard Pascal, Schmidt Christine Katrin, Vaur Sabine, Dheur Sonia, Drogat Julie, Genier Sylvie, Ekwall Karl, Uhlmann Frank, Javerzat Jean-Paul
Université Bordeaux 2, CNRS Institut de Biochimie et Génétique Cellulaires, Bordeaux, France.
EMBO J. 2008 Jan 9;27(1):111-21. doi: 10.1038/sj.emboj.7601955. Epub 2007 Dec 13.
Sister chromatid cohesion is mediated by cohesin, but the process of cohesion establishment during S-phase is still enigmatic. In mammalian cells, cohesin binding to chromatin is dynamic in G1, but becomes stabilized during S-phase. Whether the regulation of cohesin stability is integral to the process of cohesion establishment is unknown. Here, we provide evidence that fission yeast cohesin also displays dynamic behavior. Cohesin association with G1 chromosomes requires continued activity of the cohesin loader Mis4/Ssl3, suggesting that repeated loading cycles maintain cohesin binding. Cohesin instability in G1 depends on wpl1, the fission yeast ortholog of mammalian Wapl, suggestive of a conserved mechanism that controls cohesin stability on chromosomes. wpl1 is nonessential, indicating that a change in wpl1-dependent cohesin dynamics is dispensable for cohesion establishment. Instead, we find that cohesin stability increases at the time of S-phase in a reaction that can be uncoupled from DNA replication. Hence, cohesin stabilization might be a pre-requisite for cohesion establishment rather than its consequence.
姐妹染色单体黏连由黏连蛋白介导，但在S期建立黏连的过程仍不清楚。在哺乳动物细胞中，黏连蛋白与染色质的结合在G1期是动态的，但在S期变得稳定。黏连蛋白稳定性的调节是否是黏连建立过程所必需的尚不清楚。在这里，我们提供证据表明裂殖酵母黏连蛋白也表现出动态行为。黏连蛋白与G1期染色体的结合需要黏连蛋白装载因子Mis4/Ssl3的持续活性，这表明重复的装载循环维持了黏连蛋白的结合。G1期黏连蛋白的不稳定性取决于wpl1，它是哺乳动物Wapl在裂殖酵母中的同源物，提示存在一种保守机制来控制黏连蛋白在染色体上的稳定性。wpl1并非必需，这表明wpl1依赖的黏连蛋白动力学变化对于黏连建立是可有可无的。相反，我们发现黏连蛋白的稳定性在S期时增加，这一反应可与DNA复制解偶联。因此，黏连蛋白的稳定化可能是黏连建立的一个先决条件，而非其结果。
