6s2f

From Proteopedia

Cryo-EM structure of Ctf18-1-8 in complex with the catalytic domain of DNA polymerase epsilon (Class 2)

PDB ID 6s2f

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Structural highlights

6s2f is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 5.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOE_YEAST DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.^[1]

Publication Abstract from PubMed

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 . 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.

Ctf18-RFC and DNA Pol form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication.,Stokes K, Winczura A, Song B, Piccoli G, Grabarczyk DB Nucleic Acids Res. 2020 Aug 20;48(14):8128-8145. doi: 10.1093/nar/gkaa541. PMID:32585006^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shimizu K, Hashimoto K, Kirchner JM, Nakai W, Nishikawa H, Resnick MA, Sugino A. Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiae. J Biol Chem. 2002 Oct 4;277(40):37422-9. Epub 2002 Jul 17. PMID:12124389 doi:http://dx.doi.org/10.1074/jbc.M204476200
↑ Stokes K, Winczura A, Song B, Piccoli G, Grabarczyk DB. Ctf18-RFC and DNA Pol form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication. Nucleic Acids Res. 2020 Aug 20;48(14):8128-8145. doi: 10.1093/nar/gkaa541. PMID:32585006 doi:http://dx.doi.org/10.1093/nar/gkaa541