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Browsing by Author "Martinez Carranza, Markel"

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    Communication Between Dna Polymerases and Replication Protein a Within the Archaeal Replisome
    (Nature Portfolio, 2024) Martinez Carranza, Markel; Vialle, Lea; Madru, Clement; Cordier, Florence; Tekpinar, Ayten Dizkirici; Haouz, Ahmed; Sauguet, Ludovic
    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 demonstrate 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 unveil 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 is 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 central replication factors such as RPA, which regulate genome maintenance in Archaea and Eukaryotes.
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