ArticleMolecular biology of the cell2005
The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiae.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 114 citations in OpenAlex.
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- rDNA copy number variation affects yeast fitness in response to different environments.Genetics · 2025Article
- FAM43A coordinates mtDNA replication and mitochondrial biogenesis in response to mtDNA depletion.The Journal of cell biology · 2025Article
- Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA.Molecular biology of the cell · 2024Article
- Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth.Nature structural & molecular biology · 2023Article
- Prefoldin 2 contributes to mitochondrial morphology and function.BMC biology · 2023Article
- Yeast Chromatin Mutants Reveal Altered mtDNA Copy Number and Impaired Mitochondrial Membrane Potential.Journal of fungi (Basel, Switzerland) · 2023Article
- Tolerance to replication stress requires Dun1p kinase and activation of the electron transport chain.Biochimica et biophysica acta. Molecular cell research · 2023Article
- Review
- Mitochondrial DNA: cellular genotoxic stress sentinel.Trends in biochemical sciences · 2021Review
- Mitochondrial activities play a pivotal role in regulating cell cycle in response to doxorubicin.Cell cycle (Georgetown, Tex.) · 2021Article
- Mitochondrial HMG-Box Containing Proteins: From Biochemical Properties to the Roles in Human Diseases.Biomolecules · 2020Review
- Mrx6 regulates mitochondrial DNA copy number inMolecular biology of the cell · 2020Article
- Review
- Pif1 family DNA helicases: A helpmate to RNase H?DNA repair · 2019Review
- Article
- DNA damage response activates respiration and thereby enlarges dNTP pools to promote cell survival in budding yeast.The Journal of biological chemistry · 2019Article
- The plasmid-borne quinolone resistance protein QnrB, a novel DnaA-binding protein, increases the bacterial mutation rate by triggering DNA replication stress.Molecular microbiology · 2019Article
- Saccharomyces cerevisiae Mhr1 can bind Xho I-induced mitochondrial DNA double-strand breaks in vivo.Mitochondrion · 2018Article
- Autophagy balances mtDNA synthesis and degradation by DNA polymerase POLG during starvation.The Journal of cell biology · 2018Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
How mitochondrial DNA (mtDNA) copy number is determined and modulated according to cellular demands is largely unknown. Our previous investigations of the related DNA helicases Pif1p and Rrm3p uncovered a role for these factors and the conserved Mec1/Rad53 nuclear checkpoint pathway in mtDNA mutagenesis and stability in Saccharomyces cerevisiae. Here, we demonstrate another novel function of this pathway in the regulation of mtDNA copy number. Deletion of RRM3 or SML1, or overexpression of RNR1, which recapitulates Mec1/Rad53 pathway activation, resulted in an approximately twofold increase in mtDNA content relative to the corresponding wild-type yeast strains. In addition, deletion of RRM3 or SML1 fully rescued the approximately 50% depletion of mtDNA observed in a pif1 null strain. Furthermore, deletion of SML1 was shown to be epistatic to both a rad53 and an rrm3 null mutation, placing these three genes in the same genetic pathway of mtDNA copy number regulation. Finally, increased mtDNA copy number via the Mec1/Rad53 pathway could occur independently of Abf2p, an mtDNA-binding protein that, like its metazoan homologues, is implicated in mtDNA copy number control. Together, these results indicate that signaling through the Mec1/Rad53 pathway increases mtDNA copy number by altering deoxyribonucleoside triphosphate pools through the activity of ribonucleotide reductase. This comprises the first linkage of a conserved signaling pathway to the regulation of mitochondrial genome copy number and suggests that homologous pathways in humans may likewise regulate mtDNA content under physiological conditions.
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