Communication between DNA polymerases and Replication Protein A within the archaeal replisome
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 demonstrate that archaeal RPA hosts a winged-helix domain (WH) that interacts with two ke...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55365-w |
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| author | Markel Martínez-Carranza Léa Vialle Clément Madru Florence Cordier Ayten Dizkirici Tekpinar Ahmed Haouz Pierre Legrand Rémy A. Le Meur Patrick England Rémi Dulermo J. Iñaki Guijarro Ghislaine Henneke Ludovic Sauguet |
| author_facet | Markel Martínez-Carranza Léa Vialle Clément Madru Florence Cordier Ayten Dizkirici Tekpinar Ahmed Haouz Pierre Legrand Rémy A. Le Meur Patrick England Rémi Dulermo J. Iñaki Guijarro Ghislaine Henneke Ludovic Sauguet |
| author_sort | Markel Martínez-Carranza |
| collection | DOAJ |
| description | 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 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. |
| format | Article |
| id | doaj-art-39beb4e1884341698268505f4146099f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-39beb4e1884341698268505f4146099f2025-01-05T12:35:41ZengNature PortfolioNature Communications2041-17232024-12-0115111710.1038/s41467-024-55365-wCommunication between DNA polymerases and Replication Protein A within the archaeal replisomeMarkel Martínez-Carranza0Léa Vialle1Clément Madru2Florence Cordier3Ayten Dizkirici Tekpinar4Ahmed Haouz5Pierre Legrand6Rémy A. Le Meur7Patrick England8Rémi Dulermo9J. Iñaki Guijarro10Ghislaine Henneke11Ludovic Sauguet12Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Univ Brest, Ifremer, CNRS, Biologie et Ecologie des Ecoystèmes marins profonds (BEEP)Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Biological NMR & HDX-MS Technological Platform, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Crystallography Platform, C2RT, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Synchrotron SOLEIL, HelioBio group, L’Orme des MerisiersBiological NMR & HDX-MS Technological Platform, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Molecular Biophysics Platform, C2RT, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Univ Brest, Ifremer, CNRS, Biologie et Ecologie des Ecoystèmes marins profonds (BEEP)Biological NMR & HDX-MS Technological Platform, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Univ Brest, Ifremer, CNRS, Biologie et Ecologie des Ecoystèmes marins profonds (BEEP)Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528Abstract 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.https://doi.org/10.1038/s41467-024-55365-w |
| spellingShingle | Markel Martínez-Carranza Léa Vialle Clément Madru Florence Cordier Ayten Dizkirici Tekpinar Ahmed Haouz Pierre Legrand Rémy A. Le Meur Patrick England Rémi Dulermo J. Iñaki Guijarro Ghislaine Henneke Ludovic Sauguet Communication between DNA polymerases and Replication Protein A within the archaeal replisome Nature Communications |
| title | Communication between DNA polymerases and Replication Protein A within the archaeal replisome |
| title_full | Communication between DNA polymerases and Replication Protein A within the archaeal replisome |
| title_fullStr | Communication between DNA polymerases and Replication Protein A within the archaeal replisome |
| title_full_unstemmed | Communication between DNA polymerases and Replication Protein A within the archaeal replisome |
| title_short | Communication between DNA polymerases and Replication Protein A within the archaeal replisome |
| title_sort | communication between dna polymerases and replication protein a within the archaeal replisome |
| url | https://doi.org/10.1038/s41467-024-55365-w |
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