Physical interactions between MCM and Rad51 facilitate replication fork lesion bypass and ssDNA gap filling by non-recombinogenic functions
| Autor: | Macarena Morillo-Huesca, Román González-Prieto, María J. Cabello-Lobato, Aurora Yáñez-Vílchez, Juan M. Roldán-Romero, Félix Prado, Ronald P.C. Wong, María I. Cano-Linares, Marta Vicioso, Helle D. Ulrich, Cristina González-Garrido |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), German Research Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DNA Replication
replication DNA Repair QH301-705.5 genetic processes RAD52 Saccharomyces cerevisiae RAD51 DNA Single-Stranded Replication homologous recombination Origin of replication Models Biological General Biochemistry Genetics and Molecular Biology Cdc7 chemistry.chemical_compound Minichromosome maintenance Biology (General) Homologous recombination Cell Nucleus biology Cell Cycle Helicase MCM Methyl Methanesulfonate biology.organism_classification Rad52 DNA Repair and Recombination Protein Cell biology enzymes and coenzymes (carbohydrates) Solubility chemistry Multiprotein Complexes Rad52 Rad51 biology.protein DNA damage Rad51 Recombinase DNA Protein Binding |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Cell Reports, Vol 36, Iss 4, Pp 109440-(2021) Cell Reports, 36(4). CELL PRESS |
| Popis: | The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumulates in a MCM- and DNA-binding-independent manner and interacts with MCM helicases located outside of the replication origins and forks. MCM, Rad51, and Rad52 accumulate in this scaffold in G1 and are released during the S phase. In the presence of replication-blocking lesions, Cdc7 prevents their release from the scaffold, thus maintaining the interactions. We identify a rad51 mutant that is impaired in its ability to bind to MCM but not to the scaffold. This mutant is proficient in recombination but partially defective in single-stranded DNA (ssDNA) gap filling and replication fork progression through damaged DNA. Therefore, cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to assist stressed forks through non-recombinogenic functions. This work was supported by grants BFU2015-63698-P and PGC2018-099182-B-I00 (to F.P.) from the Spanish government, and project-ID 393547839-SFB1361 (to H.D.U.) from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). M.J.C.-L., M.I.C.-L., C.G.-G, A.Y.-V., and R.G.-P were recipients of pre-doctoral training grants from the Spanish government. |
| Databáze: | OpenAIRE |
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