A Mechanistic Model of Primer Synthesis from Catalytic Structures of DNA Polymerase α-primase

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2024 Mar 16

PMID 38491139

Authors

Elwood A Mullins

Lauren E Salay

Clarissa L Durie

Noah P Bradley

Jane E Jackman

Melanie D Ohi

Walter J Chazin

Brandt F Eichman

Affiliations

Soon will be listed here.

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.

Citing Articles

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Primase-polymerases: how to make a primer from scratch.

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