Unexpected new insights into DNA clamp loaders,BioEssays

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Unexpected new insights into DNA clamp loaders
BioEssays ( IF 3.2 ) Pub Date : 2022-09-18 , DOI: 10.1002/bies.202200154
Huilin Li ₁ , Mike O'Donnell _{2,

3} , Brian Kelch ₄

Affiliation

Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero-pentameric clamp loader. Eukaryotes also have three alternative RFC-like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24-RFC (Rad17-RFC in human) that loads a 9-1-1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24-RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9-1-1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism.

中文翻译：

对 DNA 钳装载机的意外新见解

夹钳加载器是五聚体 AAA+ 组件，使用 ATP 打开和关闭围绕 DNA 的圆形 DNA 滑动夹钳。从细菌到人类，夹钳装载机在所有生物体中都表现出同源性。真核 PCNA 夹通过复制因子 C (RFC) 异五聚体夹加载器加载到 3' 引发的 DNA 上。真核生物也有三种可供选择的类似 RFC 的钳位加载器 (RLC)，其中 Rfc1 亚基被另一种蛋白质取代。其中之一是酵母 Rad24-RFC（人类中的 Rad17-RFC），它将 9-1-1 异源三聚体钳夹加载到 DNA 的凹陷 5' 端。最近对 Rad24-RFC 的结构研究发现了一个意想不到的 5' DNA 结合位点位于夹具加载器的外部，并揭示了如何利用 5' 端将 9-1-1 夹具加载到 DNA 上。鉴于这些结果，新的研究表明 RFC 还包含一个 5' DNA 结合位点，在缝隙修复中发挥作用。这些研究还揭示了夹紧装载机的许多新特性。如本文所述，这些最近的研究共同改变了我们对夹紧装载机机构的看法。

更新日期：2022-09-18

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