6S2E

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

6S2E の概要

• エントリーDOI: 10.2210/pdb6s2e/pdb
• EMDBエントリー: 10088
• 分子名称: DNA polymerase epsilon catalytic subunit A, Chromosome transmission fidelity protein 8, Chromosome transmission fidelity protein 18, ... (5 entities in total)
• 機能のキーワード: dna polymerase, pcna loader, protein complex, replication
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203152.80

構造登録者

Grabarczyk, D.B.,Song, B. (登録日: 2019-06-20, 公開日: 2020-07-08, 最終更新日: 2024-07-10)

主引用文献

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

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

実験手法

ELECTRON MICROSCOPY (4.2 Å)