Physical interactions between specifically regulated subpopulations of the MCM and RNR complexes prevent genetic instability.
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 non-canonical roles in genetic stability preventing persistent Rad52 centers and hypermutagenesis.
Mesh Terms:
Cell Cycle Proteins, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, Genomic Instability, Minichromosome Maintenance Proteins, Protein Serine-Threonine Kinases, Rad52 DNA Repair and Recombination Protein, Replication Protein A, Ribonucleoside Diphosphate Reductase, Ribonucleotide Reductases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cell Cycle Proteins, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, Genomic Instability, Minichromosome Maintenance Proteins, Protein Serine-Threonine Kinases, Rad52 DNA Repair and Recombination Protein, Replication Protein A, Ribonucleoside Diphosphate Reductase, Ribonucleotide Reductases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
PLoS Genet
Date: May. 01, 2024
PubMed ID: 38776358
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