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-Structure paper
タイトル | A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 5, Page 777-790, Year 2024 |
掲載日 | 2024年3月15日 |
著者 | Elwood A Mullins / Lauren E Salay / Clarissa L Durie / Noah P Bradley / Jane E Jackman / Melanie D Ohi / Walter J Chazin / Brandt F Eichman / |
PubMed 要旨 | The mechanism by which polymerase α-primase (polα-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is ...The mechanism by which polymerase α-primase (polα-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is unknown. Here, we report cryo-EM structures of Xenopus laevis polα-primase in complex with primed templates representing various stages of DNA synthesis. Our data show how interaction of the primase regulatory subunit with the primer 5' end facilitates handoff of the primer to polα and increases polα processivity, thereby regulating both RNA and DNA composition. The structures detail how flexibility within the heterotetramer enables synthesis across two active sites and provide evidence that termination of DNA synthesis is facilitated by reduction of polα and primase affinities for the varied conformations along the chimeric primer-template duplex. Together, these findings elucidate a critical catalytic step in replication initiation and provide a comprehensive model for primer synthesis by polα-primase. |
リンク | Nat Struct Mol Biol / PubMed:38491139 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 14.06 Å |
構造データ | EMDB-29862, PDB-8g99: EMDB-29864, PDB-8g9f: EMDB-29871, PDB-8g9l: EMDB-29872, PDB-8g9n: EMDB-29873, PDB-8g9o: EMDB-29888, PDB-8v5m: EMDB-29889, PDB-8v5n: EMDB-29891, PDB-8v5o: EMDB-42140, PDB-8ucu: EMDB-42141, PDB-8ucv: EMDB-42142, PDB-8ucw: EMDB-42990, PDB-8v6g: EMDB-42991, PDB-8v6h: EMDB-42992, PDB-8v6i: EMDB-42993, PDB-8v6j: |
化合物 | ChemComp-ZN: ChemComp-SF4: ChemComp-DGT: ChemComp-MG: |
由来 |
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キーワード | REPLICATION / TRANSFERASE / Primase / DNA polymerase / chimeric RNA-DNA primer / RNA/DNA hybrid / DNA replication / DNA synthesis / TRANSFERASE/DNA/RNA / TRANSFERASE-DNA-RNA complex |