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Ctf18-RFC and DNA Pol ϵ form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication
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Stokes, Katherine, Winczura, Alicja, Song, Boyuan, De Piccoli, Giacomo and Grabarczyk, Daniel B. (2020) Ctf18-RFC and DNA Pol ϵ form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication. Nucleic Acids Research, 48 (14). pp. 8128-8145. doi:10.1093/nar/gkaa541
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WRAP-Ctf18-RFC-DNA-Polymerase-epsilon-leading-strand polymerase-clamp-DNA-replication-De-Piccoli-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (9Mb) | Preview |
Official URL: https://doi.org/10.1093/nar/gkaa541
Abstract
The eukaryotic replisome must faithfully replicate DNA and cope with replication fork blocks and stalling, while simultaneously promoting sister chromatid cohesion. Ctf18-RFC is an alternative PCNA loader that links all these processes together by an unknown mechanism. Here, we use integrative structural biology combined with yeast genetics and biochemistry to highlight the specific functions that Ctf18-RFC plays within the leading strand machinery via an interaction with the catalytic domain of DNA Pol ϵ. We show that a large and unusually flexible interface enables this interaction to occur constitutively throughout the cell cycle and regardless of whether forks are replicating or stalled. We reveal that, by being anchored to the leading strand polymerase, Ctf18-RFC can rapidly signal fork stalling to activate the S phase checkpoint. Moreover, we demonstrate that, independently of checkpoint signaling or chromosome cohesion, Ctf18-RFC functions in parallel to Chl1 and Mrc1 to protect replication forks and cell viability. [Abstract copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.]
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | |||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | DNA replication, DNA polymerases, Proliferating cell nuclear antigen | |||||||||
| Journal or Publication Title: | Nucleic Acids Research | |||||||||
| Publisher: | Oxford University Press | |||||||||
| ISSN: | 0305-1048 | |||||||||
| Official Date: | 25 June 2020 | |||||||||
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| Date of first compliant deposit: | 2 September 2020 | |||||||||
| Volume: | 48 | |||||||||
| Number: | 14 | |||||||||
| Page Range: | pp. 8128-8145 | |||||||||
| DOI: | 10.1093/nar/gkaa541 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| RIOXX Funder/Project Grant: |
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