Communication between DNA polymerases and Replication Protein A within the archaeal replisome - Archive ouverte HAL
Preprints, Working Papers, ... Year : 2024

Communication between DNA polymerases and Replication Protein A within the archaeal replisome

Pierre Legrand

Abstract

Replication Protein A (RPA) plays a pivotal role in DNA replication by coating and protecting exposed single-stranded DNA, and acting as a molecular hub that recruits additional replication factors. We demonstrated that archaeal RPA hosts a winged-helix domain (WH) that interacts with two key actors of the replisome: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). Using an integrative structural biology approach, combining nuclear magnetic resonance, X-ray crystallography and cryo-electron microscopy, we unveiled how RPA interacts with PriSL and PolD through two distinct surfaces of the WH domain: an evolutionarily conserved interface and a novel binding site. Finally, RPA was shown to stimulate the activity of PriSL in a WH-dependent manner. This study provides a molecular understanding of the WH-mediated regulatory activity in conserved central replication factors such as RPA, which regulate genome maintenance in Archaea and Eukaryotes.

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hal-04728470 , version 1 (09-10-2024)

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Markel Martínez-Carranza, Léa Vialle, Clément Madru, Florence Cordier, Ayten Dizkirici Tekpinar, et al.. Communication between DNA polymerases and Replication Protein A within the archaeal replisome. 2024. ⟨hal-04728470⟩
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