Article
Physical interactions between specifically regulated subpopulations of the MCM and RNR complexes prevent genetic instability
Author/s | Yáñez Vilches, Aurora
Romero, Antonia M. Barrientos Moreno, Marta Cruz, Esther González Prieto, Román Sharma, Sushma Vertegaal, Alfred C.O. Prado, Félix |
Department | Universidad de Sevilla. Departamento de Biología Celular |
Publication Date | 2024-05-22 |
Deposit Date | 2024-06-18 |
Published in |
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Abstract | The helicase MCM and the ribonucleotide reductase RNR are the complexes that provide the substrates (ssDNA templates and dNTPs, respectively) for DNA replication. Here, we demonstrate that MCM interacts physically with RNR ... The helicase MCM and the ribonucleotide reductase RNR are the complexes that provide the substrates (ssDNA templates and dNTPs, respectively) for DNA replication. Here, we demonstrate that MCM interacts physically with RNR and some of its regulators, including the kinase Dun1. These physical interactions encompass small subpopulations of MCM and RNR, are independent of the major subcellular locations of these two complexes, augment in response to DNA damage and, in the case of the Rnr2 and Rnr4 subunits of RNR, depend on Dun1. Partial disruption of the MCM/RNR interactions impairs the release of Rad52 -but not RPA-from the DNA repair centers despite the lesions are repaired, a phenotype that is associated with hypermutagenesis but not with alterations in the levels of dNTPs. These results suggest that a specifically regulated pool of MCM and RNR complexes plays noncanonical roles in genetic stability preventing persistent Rad52 centers and hypermutagenesis. |
Citation | Yáñez Vilches, A., Romero, A.M., Barrientos Moreno, M., Cruz, E., González Prieto, R., Sharma, S.,...,Prado, F. (2024). Physical interactions between specifically regulated subpopulations of the MCM and RNR complexes prevent genetic instability. PLoS Genetics, 20 (5), e1011148. https://doi.org/10.1371/journal.pgen.1011148. |
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