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首页> 外文期刊>Molecular and Cellular Biology >Mechanical Link between Cohesion Establishment and DNA Replication: Ctf7p/Eco1p, a Cohesion Establishment Factor, Associates with Three Different Replication Factor C Complexes
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Mechanical Link between Cohesion Establishment and DNA Replication: Ctf7p/Eco1p, a Cohesion Establishment Factor, Associates with Three Different Replication Factor C Complexes

机译:内聚建立和DNA复制之间的机械联系:内聚建立因子Ctf7p / Eco1p与三种不同的复制因子C复合体相关联

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CTF7/ECO1 is an essential yeast gene required for the establishment of sister chromatid cohesion. The findings that CTF7/ECO1, POL30 (PCNA), and CHL12/CTF18 (a replication factor C [RFC] homolog) genetically interact provided the first evidence that the processes of cohesion establishment and DNA replication are intimately coupled—a link now confirmed by other studies. To date, however, it is unknown how Ctf7p/Eco1p function is coupled to DNA replication or whether Ctf7p/Eco1p physically associates with any components of the DNA replication machinery. Here, we report that Ctf7p/Eco1p associates with proteins that perform partially redundant functions in DNA replication. Chl12p/Ctf18p combines with Rfc2p to Rfc5p to form one of three independent RFC complexes. By chromatographic methods, Ctf7p/Eco1p was found to associate with Chl12/Ctf18p and with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. The association between Ctf7p/Eco1p and this RFC complex is biologically relevant in that (i) Ctf7p/Eco1p cosediments with Chl12p/Ctf18p in vivo and (ii) rfc5-1 mutant cells exhibit precocious sister separation. Previous studies revealed that Rfc1p or Rad24p associates with Rfc2p to Rfc5p to form two other RFC complexes independent of Ctf18p-RFC complexes. These Rfc1p-RFC and Rad24p-RFC complexes function in DNA replication or repair and DNA damage checkpoint pathways. Importantly, Ctf7p/Eco1p also associates with Rfc1p and Rad24p, suggesting that these RFC complexes also play critical roles in cohesion establishment. The associations between Ctf7p/Eco1p and RFC subunits provide novel evidence regarding the physical linkage between cohesion establishment and DNA replication. Furthermore, the association of Ctf7p/Eco1p with each of three RFC complexes supplies new insights into the functional redundancy of RFC complexes in cohesion establishment.
机译: CTF7 / ECO1 是建立姐妹染色单体凝聚力所需的必需酵母基因。 CTF7 / ECO1 POL30 (PCNA)和 CHL12 / CTF18 (复制因子C [RFC]同源物)发生遗传相互作用的发现提供了凝聚力建立和DNA复制过程紧密耦合的第一个证据-其他研究现在证实了这一联系。但是,迄今为止,尚不清楚Ctf7p / Eco1p功能如何与DNA复制耦合,或者Ctf7p / Eco1p是否在物理上与DNA复制机制的任何组件相关联。在这里,我们报告Ctf7p / Eco1p与在DNA复制中执行部分冗余功能的蛋白质缔合。 Chl12p / Ctf18p与Rfc2p到Rfc5p结合形成三个独立的RFC复合体之一。通过色谱方法,发现Ctf7p / Eco1p与Chl12 / Ctf18p以及Rfc2p,Rfc3p,Rfc4p和Rfc5p缔合。 Ctf7p / Eco1p与该RFC复合体之间的关联在生物学上具有相关性,因为(i)Ctf7p / Eco1p与Chl12p / Ctf18p在体内的共沉淀和(ii) rfc5 - 1 突变体细胞表现出早熟的姐妹分离。先前的研究表明,Rfc1p或Rad24p与Rfc2p关联到Rfc5p可以形成两个独立于Ctf18p-RFC复合物的RFC复合物。这些Rfc1p-RFC和Rad24p-RFC复合物在DNA复制或修复以及DNA损伤检查点途径中起作用。重要的是,Ctf7p / Eco1p也与Rfc1p和Rad24p相关联,表明这些RFC复合体在建立内聚力中也起着关键作用。 Ctf7p / Eco1p与RFC亚基之间的关联为凝聚力建立和DNA复制之间的物理联系提供了新的证据。此外,Ctf7p / Eco1p与三个RFC复合体中的每一个的关联为凝聚建立中RFC复合体的功能冗余提供了新的见解。

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