Ctf18-RFC is an alternative PCNA loader which plays important but poorly understood roles in multiple DNA replication-associated processes. To fulfill its specialist roles, the Ctf18-RFC clamp loader contains a unique module in which the Dcc1-Ctf8 complex is bound to the C terminus of Ctf18 (the Ctf18-1-8 module). Here, we report the structural and functional characterization of the heterotetrameric complex formed between Ctf18-1-8 and a 63 kDa fragment of DNA polymerase ɛ. Our data reveal that Ctf18-1-8 binds stably to the polymerase and far from its other functional sites, suggesting that Ctf18-RFC could be associated with Pol ɛ throughout normal replication as the leading strand clamp loader. We also show that Pol ɛ and double-stranded DNA compete to bind the same winged-helix domain on Dcc1, with Pol ɛ being the preferred binding partner, thus suggesting that there are two alternative pathways to recruit Ctf18-RFC to sites of replication.

中文翻译：

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招聘Ctf18-RFC到复制体的结构基础。

Ctf18-RFC是一种替代的PCNA加载程序，在与DNA复制相关的多个过程中扮演着重要的角色，但人们对其了解甚少。为了履行其专家职责，Ctf18-RFC钳位加载器包含一个独特的模块，其中Dcc1-Ctf8复合体绑定到Ctf18的C端（Ctf18-1-8模块）。在这里，我们报道了在Ctf18-1-8和DNA聚合酶a的一个63 kDa片段之间形成的异四聚体复合物的结构和功能表征。我们的数据表明，Ctf18-1-8稳定地与聚合酶结合，并且远离其其他功能位点，这表明Ctf18-RFC可能在整个正常复制过程中作为前导链钳装载器与Pol associated相关。我们还显示，Polɛ和双链DNA竞争结合Dcc1上相同的有翼螺旋结构域，其中Polɛ是首选的结合伴侣，