A screen for cohesion mutants uncovers ss13, the fission yeast counterpart of the cohesin loading factor Scc4
A screen for cohesion mutants uncovers ss13, the fission yeast counterpart of the cohesin loading factor Scc4
复制标题
DOI：
10.1016/j.cub.2006.03.037
复制
发表时间：
2006-05-09
期刊：
影响因子：
9.2
通讯作者：
Javerzat, Jean-Paul
中科院分区：
文献类型：
--
作者：
Bernard, Pascal;Drogat, Julie;Javerzat, Jean-Paul
姐妹染色单体凝聚是由粘附素介导的，粘附素是由酿酒酵母中的四个核心亚基Scc1、Scc3、Smc1和Smc3(裂殖酵母中的Rad21、Psc3、Psm1和PSM3)组成的环状复合体。粘附素如何确保凝聚力尚不清楚，尽管它的环形形状表明它可能通过包围姐妹DNA链来拴住它们[1]。凝聚力的建立是一个分两步走的过程。粘附素在复制之前被加载到染色体上，随后在S时期建立了凝聚力。在酿酒酵母中，粘附素的装载需要一个单独的包含Scc2和Scc4蛋白的复合体。当Scc2受损时，粘附素环不能与染色质结合，凝聚力也不能建立[2]。负载的机制尚不清楚，尽管一些数据表明与Smc1/3结合的ATP需要水解[3，4]。Scc2同源物存在于裂解酵母(Mis4)、果蝇、非洲爪哇和人类中[5-10]。相比之下，到目前为止还没有鉴定出Scc4的同源基因。我们在此报道了裂解酵母ssl3作为Scc4样因子的鉴定。Ssl3与Mis4是一个复合体，作为一种真正的负载因子，ssl3在G1中是粘附素与染色体结合所必需的，但在G2中是不可缺少的，当凝聚力建立时。Scc4功能同源物的发现表明，粘附素的装载机制在真核生物中是保守的。
Sister-chromatid cohesion is mediated by cohesin, a ring-shape complex made of four core subunits called Scc1, Scc3, Smc1, and Smc3 in Saccharomyces cerevisiae (Rad21, Psc3, Psm1, and Psm3 in Schizosaccharomyces pombe). How cohesin ensures cohesion is unknown, although its ring shape suggests that it may tether sister DNA strands by encircling them [1]. Cohesion establishment is a two-step process. Cohesin is loaded on chromosomes before replication and cohesion is subsequently established during S phase. In S. cerevisiae, cohesin loading requires a separate complex containing the Scc2 and Scc4 proteins. Cohesin rings fail to associate with chromatin and cohesion can not establish when Scc2 is impaired [2]. The mechanism of loading is unknown, although some data suggest that hydrolysis of ATP bound to Smc1/3 is required [3, 4]. Scc2 homologs exist in fission yeast (Mis4), Drosophila, Xenopus, and human [5-10]. By contrast, no homolog of Scc4 has been identified so far. We report here on the identification of fission yeast Ssl3 as a Scc4-like factor. Ssl3 is in complex with Mis4 and, as a bona fide loading factor, Ssl3 is required in G1 for cohesin binding to chromosomes but dispensable in G2 when cohesion is established. The discovery of a functional homolog of Scc4 indicates that the machinery of cohesin loading is conserved among eukaryotes.