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6S2E

Cryo-EM structure of Ctf18-1-8 in complex with the catalytic domain of DNA polymerase epsilon

Summary for 6S2E
Entry DOI10.2210/pdb6s2e/pdb
EMDB information10088
DescriptorDNA polymerase epsilon catalytic subunit A, Chromosome transmission fidelity protein 8, Chromosome transmission fidelity protein 18, ... (5 entities in total)
Functional Keywordsdna polymerase, pcna loader, protein complex, replication
Biological sourceSaccharomyces cerevisiae S288C
More
Total number of polymer chains4
Total formula weight203152.80
Authors
Grabarczyk, D.B.,Song, B. (deposition date: 2019-06-20, release date: 2020-07-08, Last modification date: 2024-07-10)
Primary citationStokes, K.,Winczura, A.,Song, B.,Piccoli, G.,Grabarczyk, D.B.
Ctf18-RFC and DNA Pol ε form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication.
Nucleic Acids Res., 48:8128-8145, 2020
Cited by
PubMed 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.
PubMed: 32585006
DOI: 10.1093/nar/gkaa541
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (4.2 Å)
Structure validation

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