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Ctf18-RFC介导的增殖细胞核抗原（PCNA）加载机制用于前导链DNA合成。

Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis.

作者信息

Yuan Zuanning, Georgescu Roxana, Yao Nina Y, Yurieva Olga, O'Donnell Michael E, Li Huilin

机构信息

Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.

DNA Replication Laboratory, The Rockefeller University, New York, NY, USA.

出版信息

Science. 2024 Aug 2;385(6708):eadk5901. doi: 10.1126/science.adk5901.

DOI:10.1126/science.adk5901
PMID:39088616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349045/
Abstract

The proliferating cell nuclear antigen (PCNA) clamp encircles DNA to hold DNA polymerases (Pols) to DNA for processivity. The Ctf18-RFC PCNA loader, a replication factor C (RFC) variant, is specific to the leading-strand Pol (Polε). We reveal here the underlying mechanism of Ctf18-RFC specificity to Polε using cryo-electron microscopy and biochemical studies. We found that both Ctf18-RFC and Polε contain specific structural features that direct PCNA loading onto DNA. Unlike other clamp loaders, Ctf18-RFC has a disordered ATPase associated with a diverse cellular activities (AAA+) motor that requires Polε to bind and stabilize it for efficient PCNA loading. In addition, Ctf18-RFC can pry prebound Polε off of DNA, then load PCNA onto DNA and transfer the PCNA-DNA back to Polε. These elements in both Ctf18-RFC and Polε provide specificity in loading PCNA onto DNA for Polε.

摘要

增殖细胞核抗原（PCNA）夹子环绕DNA，将DNA聚合酶（Pols）固定在DNA上以实现持续合成能力。Ctf18 - RFC PCNA装载因子是复制因子C（RFC）的变体，对前导链Pol（Polε）具有特异性。我们在此利用冷冻电子显微镜和生化研究揭示了Ctf18 - RFC对Polε具有特异性的潜在机制。我们发现Ctf18 - RFC和Polε都含有将PCNA装载到DNA上的特定结构特征。与其他夹子装载因子不同，Ctf18 - RFC具有与多种细胞活动相关的无序ATP酶（AAA +）马达，该马达需要Polε结合并稳定它以实现高效的PCNA装载。此外，Ctf18 - RFC可以将预先结合的Polε从DNA上撬开，然后将PCNA装载到DNA上，并将PCNA - DNA转移回Polε。Ctf18 - RFC和Polε中的这些元件在将PCNA装载到DNA上以用于Polε时提供了特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/77f81222fe8d/nihms-2014923-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/3d20efb83492/nihms-2014923-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/2ae0b5ff0d69/nihms-2014923-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/2e66352d86f5/nihms-2014923-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/c57b1f6fdb91/nihms-2014923-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/6c27daf4e708/nihms-2014923-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/77f81222fe8d/nihms-2014923-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/3d20efb83492/nihms-2014923-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/2ae0b5ff0d69/nihms-2014923-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/2e66352d86f5/nihms-2014923-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/c57b1f6fdb91/nihms-2014923-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/6c27daf4e708/nihms-2014923-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd98/11349045/77f81222fe8d/nihms-2014923-f0006.jpg

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