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A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.
Mullins, Elwood A; Salay, Lauren E; Durie, Clarissa L; Bradley, Noah P; Jackman, Jane E; Ohi, Melanie D; Chazin, Walter J; Eichman, Brandt F.
Afiliación
  • Mullins EA; Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
  • Salay LE; Center for Structural Biology, Vanderbilt University, Nashville, TN, USA.
  • Durie CL; Center for Structural Biology, Vanderbilt University, Nashville, TN, USA.
  • Bradley NP; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Jackman JE; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Ohi MD; Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Chazin WJ; Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
  • Eichman BF; Department of Biochemistry, University of Missouri, Columbia, MO, USA.
Nat Struct Mol Biol ; 31(5): 777-790, 2024 May.
Article en En | MEDLINE | ID: mdl-38491139
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Xenopus laevis / Modelos Moleculares / ADN Primasa / Microscopía por Crioelectrón / ADN Polimerasa I / Replicación del ADN Límite: Animals Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Xenopus laevis / Modelos Moleculares / ADN Primasa / Microscopía por Crioelectrón / ADN Polimerasa I / Replicación del ADN Límite: Animals Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos