Flexible tethering of primase and DNA Pol α in the eukaryotic primosome
| Autor: | Mairi L. Kilkenny, Eva Nogales, Rafael Núñez-Ramírez, Luca Pellegrini, Oscar Llorca, Rajika L. Perera, Begoña García-Alvarez, Sebastian Klinge, Roberto Melero, María Ángeles Recuero-Checa, Richard Hall, Ludovic Sauguet |
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| Přispěvatelé: | Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Cambridge [UK] (CAM), University of California, Spanish Ministry of Science and Innovation (SAF2008-00451 to O.L.), the ‘Red Temática de Investigación Cooperativa en Cáncer (RTICC)’ from the ‘Instituto de Salud Carlos III’ (RD06/0020/1001 to O.L.), the Human Frontiers Science Program (RGP39/2008 to O.L. and E.N.), a Wellcome Trust Senior Fellowship award in Basic Biomedical Sciences (to L.P.), a FPI fellowship from the Spanish Ministry of Science and Innovation to MAR-C, a JAE-DOC contract of the ‘Consejo Superior de Investigaciones Científicas (CSIC)’ and a ‘Juan de la Cierva’ contract from the Spanish Ministry of Science to BGA, EN is a Howard Hughes Medical Institute Investigator. Funding for open access charge: Spanish Ministry of Science and Innovation (SAF2008-00451 to O.L.)., Kilkenny, Mairi [0000-0002-7280-8522], Pellegrini, Luca [0000-0002-9300-497X], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular dnaI MESH: Amino Acid Sequence chemistry.chemical_compound Models Structural Biology Polymerase Genetics 0303 health sciences biology 030302 biochemistry & molecular biology Biological Sciences MESH: Protein Subunits MESH: Saccharomyces cerevisiae 3. Good health Cell biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] MESH: DNA Primase Primase Corrigendum MESH: Models Molecular [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] Saccharomyces cerevisiae Molecular Sequence Data [SDV.BC]Life Sciences [q-bio]/Cellular Biology DNA Primase Primosome 03 medical and health sciences MESH: RNA Information and Computing Sciences [CHIM.CRIS]Chemical Sciences/Cristallography [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence 030304 developmental biology MESH: DNA Polymerase I MESH: Molecular Sequence Data Molecular biology.organism_classification DNA Polymerase I Protein Subunits chemistry biology.protein RNA Primer (molecular biology) DNA polymerase I [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] Environmental Sciences DNA Developmental Biology |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2011, 39 (18), pp.8187-8199. ⟨10.1093/nar/gkr534⟩ Nucleic acids research, vol 39, iss 18 Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkr534⟩ |
| Popis: | 13 páginas, 7 figuras -- PAGS nros. 8187-8199 Núñez-Ramírez, Rafael et al. The Pol α/primase complex or primosome is the primase/polymerase complex that initiates nucleic acid synthesis during eukaryotic replication. Within the primosome, the primase synthesizes short RNA primers that undergo limited extension by Pol α. The resulting RNA–DNA primers are utilized by Pol δ and Pol ε for processive elongation on the lagging and leading strands, respectively. Despite its importance, the mechanism of RNA–DNA primer synthesis remains poorly understood. Here, we describe a structural model of the yeast primosome based on electron microscopy and functional studies. The 3D architecture of the primosome reveals an asymmetric, dumbbell-shaped particle. The catalytic centers of primase and Pol α reside in separate lobes of high relative mobility. The flexible tethering of the primosome lobes increases the efficiency of primer transfer between primase and Pol α. The physical organization of the primosome suggests that a concerted mechanism of primer hand-off between primase and Pol α would involve coordinated movements of the primosome lobes. The first three-dimensional map of the eukaryotic primosome at 25 Å resolution provides an essential structural template for understanding initiation of eukaryotic replication Spanish Ministry of Science and Innovation (SAF2008-00451 to O.L.); the ‘Red Temática de Investigación Cooperativa en Cáncer (RTICC)’ from the ‘Instituto de Salud Carlos III’ (RD06/0020/1001 to O.L.); the Human Frontiers Science Program (RGP39/2008 to O.L. and E.N.); a Wellcome Trust Senior Fellowship award in Basic Biomedical Sciences (to L.P.); a FPI fellowship from the Spanish Ministry of Science and Innovation to MAR-C; a JAE-DOC contract of the ‘Consejo Superior de Investigaciones Científicas (CSIC)’ and a ‘Juan de la Cierva’ contract from the Spanish Ministry of Science to BGA; EN is a Howard Hughes Medical Institute Investigator. Funding for open access charge: Spanish Ministry of Science and Innovation (SAF2008-00451 to O.L.) |
| Databáze: | OpenAIRE |
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