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Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts

机译:复制体进展复合体将DNA复制与非洲爪蟾卵提取物中的姊妹染色单体凝聚力联系起来

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Cohesin-mediated sister chromatid cohesion is established during the S-phase, and recent studies demonstrate that a cohesin protein ring concatenates sister DNA molecules. However, little is known about how DNA replication is linked to the establishment of sister chromatid cohesion. Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts. Immunodepletion of both AND-1 and Tim1-Tipin from the extracts leads to aberrant sister chromatid cohesion, which is similarly induced by the depletion of cohesin. These results demonstrate that AND-1 and Tim1-Tipin are key factors linking DNA replication and establishment of sister chromatid cohesion. On the basis of the physical interactions between AND-1 and DNA polymerases, we discuss a model to describe how replisome progression complex establishes sister chromatid cohesion.
机译:黏着蛋白介导的姊妹染色单体凝聚力在S期建立,最近的研究表明,黏着素蛋白环连接了姊妹DNA分子。但是,关于DNA复制如何与姐妹染色单体内聚力建立联系还知之甚少。在这里,我们使用非洲爪蟾卵提取物显示,酿酒酵母Ctf4和Tof1-Csm3的同系物AND-1和Tim1-Tipin与复制体相关,并且是正确建立M相中所观察到的内聚力所必需的提取物。提取物中AND-1和Tim1-Tipin的免疫耗竭会导致姐妹染色单体凝聚异常,这同样由粘附素的消耗引起。这些结果表明,AND-1和Tim1-Tipin是连接DNA复制和姐妹染色单体内聚力建立的关键因素。在AND-1和DNA聚合酶之间的物理相互作用的基础上,我们讨论了一个模型,以描述复制性进展复合物如何建立姐妹染色单体的内聚力。

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