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-Structure paper
タイトル | Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Year 2024 |
掲載日 | 2024年8月7日 |
![]() | Johann J Roske / Joseph T P Yeeles / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 3.3 - 4.2 Å |
構造データ | EMDB-50222, PDB-9f6d: EMDB-50223, PDB-9f6e: EMDB-50224, PDB-9f6f: EMDB-50225, PDB-9f6i: EMDB-50226, PDB-9f6j: EMDB-50227, PDB-9f6k: EMDB-50228, PDB-9f6l: |
化合物 | ![]() ChemComp-SF4: ![]() ChemComp-DDS: ![]() ChemComp-MG: ![]() ChemComp-CA: |
由来 |
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![]() | REPLICATION / DNA / polymerase / epsilon / PCNA / leading strand / human / replisome / proofreading |