6S2F
Cryo-EM structure of Ctf18-1-8 in complex with the catalytic domain of DNA polymerase epsilon (Class 2)
Summary for 6S2F
| Entry DOI | 10.2210/pdb6s2f/pdb |
| EMDB information | 10088 10089 |
| Descriptor | DNA polymerase epsilon catalytic subunit A, Chromosome transmission fidelity protein 8, Chromosome transmission fidelity protein 18, ... (5 entities in total) |
| Functional Keywords | dna polymerase, pcna loader, protein complex, replication |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) More |
| Total number of polymer chains | 4 |
| Total formula weight | 203931.69 |
| Authors | Grabarczyk, D.B.,Song, B. (deposition date: 2019-06-20, release date: 2020-07-08, Last modification date: 2024-05-22) |
| Primary citation | Stokes, 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: 32585006DOI: 10.1093/nar/gkaa541 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.8 Å) |
Structure validation
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