9F6E

Human DNA polymerase epsilon bound to DNA and PCNA (ajar conformation)

9F6E の概要

• エントリーDOI: 10.2210/pdb9f6e/pdb
• EMDBエントリー: 50223
• 分子名称: DNA polymerase epsilon catalytic subunit A, Proliferating cell nuclear antigen, DNA nascent strand, ... (6 entities in total)
• 機能のキーワード: dna, polymerase, epsilon, pcna, leading strand, human, replication, replisome, proofreading
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 244459.96

構造登録者

Roske, J.J.,Yeeles, J.T.P. (登録日: 2024-05-01, 公開日: 2024-08-07, 最終更新日: 2024-12-25)

主引用文献

Roske, J.J.,Yeeles, J.T.P.
Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol epsilon.
Nat.Struct.Mol.Biol., 31:1921-1931, 2024

PubMed Abstract: During chromosome replication, the nascent leading strand is synthesized by DNA polymerase epsilon (Pol ε), which associates with the sliding clamp processivity factor proliferating cell nuclear antigen (PCNA) to form a processive holoenzyme. For high-fidelity DNA synthesis, Pol ε relies on nucleotide selectivity and its proofreading ability to detect and excise a misincorporated nucleotide. Here, we present cryo-electron microscopy (cryo-EM) structures of human Pol ε in complex with PCNA, DNA and an incoming nucleotide, revealing how Pol ε associates with PCNA through its PCNA-interacting peptide box and additional unique features of its catalytic domain. Furthermore, by solving a series of cryo-EM structures of Pol ε at a mismatch-containing DNA, we elucidate how Pol ε senses and edits a misincorporated nucleotide. Our structures delineate steps along an intramolecular switching mechanism between polymerase and exonuclease activities, providing the basis for a proofreading mechanism in B-family replicative polymerases.

PubMed: 39112807
DOI: 10.1038/s41594-024-01370-y

実験手法

ELECTRON MICROSCOPY (3.74 Å)