Establishment of sister chromatid cohesion at the S-cerevisiae replication fork

Establishment of sister chromatid cohesion at the S-cerevisiae replication fork
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DOI:
10.1016/j.molcel.2006.08.018
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发表时间:
2006-09-15
期刊:
影响因子:
16
通讯作者:
Uhlmann, Frank
Uhlmann, Frank
中科院分区:
生物学1区
文献类型:
--
作者:
Lengronne, Armelle;McIntyre, John;Uhlmann, Frank

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真核染色体的两个相同的姐妹拷贝在S期合成。为了便于在有丝分裂中将它们识别为分离的对,姐妹染色单体从它们的合成开始就通过染色体粘附素复合物保持在一起。复制叉的进展被认为与姐妹染色单体凝聚力的建立相关联,有助于复制产物的鉴定,但这方面的证据仍然是间接的。在这里,我们表明,姐妹染色单体凝聚所需的三种蛋白质,Eco1,Ctf4,和Ctf18,被发现,和Ctf4旅行沿着染色体,复制叉。在ATP水解依赖性反应中,环状粘着蛋白复合物在S期之前装载到染色体上。在DNA复制过程中的凝聚力的建立没有进一步的凝聚素招募,也不需要凝聚素重新参与ATP水解基序,这是其初始DNA结合的关键。这为复制分叉上下文中的内聚建立提供了证据,并对所涉及的机制施加了约束。
Two identical sister copies of eukaryotic chromosomes are synthesized during S phase. To facilitate their recognition as pairs for segregation in mitosis, sister chromatids are held together from their synthesis onward by the chromosomal cohesin complex. Replication fork progression is thought to be coupled to establishment of sister chromatid cohesion, facilitating identification of replication products, but evidence for this has remained circumstantial. Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks. The ring-shaped cohesin complex is loaded onto chromosomes before S phase in an ATP hydrolysis-dependent reaction. Cohesion establishment during DNA replication follows without further cohesin recruitment and without need for cohesin to reengage an ATP hydrolysis motif that is critical for its initial DNA binding. This provides evidence for cohesion establishment in the context of replication forks and imposes constraints on the mechanism involved.