Communication between DNA polymerases and Replication Protein A within the archaeal replisome
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.
Authors
- Pierre Legrand (ORCID: https://orcid.org/0000-0003-2431-2255)
- Ludovic Sauguet (ORCID: https://orcid.org/0000-0002-1259-6601)
- J. Iñaki Guijarro (ORCID: https://orcid.org/0000-0002-3826-5245)
- Clément Madru (ORCID: https://orcid.org/0000-0002-5412-8822)
- Florence Cordier (ORCID: https://orcid.org/0000-0002-5963-7773)
- Ghislaine Henneke (ORCID: https://orcid.org/0000-0002-2985-5526)
- Ahmed Haouz (ORCID: https://orcid.org/0000-0003-1196-1635)
- Patrick England (ORCID: https://orcid.org/0000-0001-6410-5918)
- Rémy Le Meur (ORCID: https://orcid.org/0000-0002-9761-4863)
- Ayten Dizkırıcı (ORCID: https://orcid.org/0000-0002-0578-5092)
- Rémi Dulermo (ORCID: https://orcid.org/0000-0002-4450-7482)
- Markel Martínez‐Carranza (ORCID: https://orcid.org/0000-0003-0192-9762)
- Léa Vialle
Institutions
- Van Yüzüncü Yıl Üniversitesi (TR)
- Centre National de la Recherche Scientifique (FR)
- Ifremer (FR)
- Institut Pasteur (FR)
- Université de Bretagne Occidentale (FR)
- Université Paris Cité (FR)
- Synchrotron soleil (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55365-w
- Citations
- 5
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale