7PMN

S. cerevisiae replisome-SCF(Dia2) complex bound to double-stranded DNA (conformation II)

これはPDB形式変換不可エントリーです。

7PMN の概要

• エントリーDOI: 10.2210/pdb7pmn/pdb
• EMDBエントリー: 13539
• 分子名称: DNA replication licensing factor MCM2, DNA replication complex GINS protein SLD5, Cell division control protein 45,Cell division control protein 45, ... (23 entities in total)
• 機能のキーワード: genome stability, dna replication, ubiquitination, termination, replisome, cryo-em, cmg, scf(dia2), replication
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 1811448.40

構造登録者

Jenkyn-Bedford, M.,Yeeles, J.T.P.,Deegan, T.D. (登録日: 2021-09-02, 公開日: 2021-11-10, 最終更新日: 2024-07-17)

主引用文献

Jenkyn-Bedford, M.,Jones, M.L.,Baris, Y.,Labib, K.P.M.,Cannone, G.,Yeeles, J.T.P.,Deegan, T.D.
A conserved mechanism for regulating replisome disassembly in eukaryotes.
Nature, 600:743-747, 2021

PubMed Abstract: Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCF in budding yeast, CUL2 in metazoa), replisome disassembly is governed by a common regulatory principle, in which ubiquitylation of CMG is suppressed before replication termination, to prevent replication fork collapse. Recent evidence suggests that this suppression is mediated by replication fork DNA. However, it is unknown how SCF and CUL2 discriminate terminated from elongating replisomes, to selectively ubiquitylate CMG only after termination. Here we used cryo-electron microscopy to solve high-resolution structures of budding yeast and human replisome-E3 ligase assemblies. Our structures show that the leucine-rich repeat domains of Dia2 and LRR1 are structurally distinct, but bind to a common site on CMG, including the MCM3 and MCM5 zinc-finger domains. The LRR-MCM interaction is essential for replisome disassembly and, crucially, is occluded by the excluded DNA strand at replication forks, establishing the structural basis for the suppression of CMG ubiquitylation before termination. Our results elucidate a conserved mechanism for the regulation of replisome disassembly in eukaryotes, and reveal a previously unanticipated role for DNA in preserving replisome integrity.

PubMed: 34700328
DOI: 10.1038/s41586-021-04145-3

実験手法

ELECTRON MICROSCOPY (3.2 Å)