Pasteur Institute, Paris "Communication between DNA polymerases and Replication Protein A within the archaeal replisome."
Nature communications 15, 10926 (2024). DOI: 10.1038/s41467-024-55365-w AuteursMartinez-Carranza M*, Vialle L*, Madru C*, Cordier F*, Tekpinar AD, Haouz A, Legrand P, Le Meur RA, England P, Dulermo R, Guijarro IJ, Henneke G, Sauguet L.
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Markel, 32 years old, did his PhD studies in the laboratory of Pål Stenmark at Stockholm University (Sweden), where he studied botulinum neurotoxins and their interactions with neuronal receptors. After his thesis defense in 2020, he worked as cryo-EM application expert at Lund University (Sweden) while studying deoxyribonucleotide biosynthesis regulation in bacteria. Since November 2021, he is a postdoctoral fellow in the DNA replication group led by Ludovic Sauguet at Institut Pasteur, where he is interested in characterizing the DNA replication machinery in Archaea with an integrative structural biology approach.
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Department of Structural Biology and Chemistry
Institut Pasteur
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Résumé de l'article
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.
