ArticleGenes & development2015
Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
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- A high-resolution, nanopore-based artificial intelligence assay for DNA replication stress in human cancer cells.Nature communications · 2025Article
- Intrinsic PARG inhibitor sensitivity is mimicked byNAR cancer · 2024Article
- Progerin Can Induce DNA Damage in the Absence of Global Changes in Replication or Cell Proliferation.bioRxiv : the preprint server for biology · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- Progerin can induce DNA damage in the absence of global changes in replication or cell proliferation.PloS one · 2024Article
- Integrated multi-omics approach revealed cellular senescence landscape.Nucleic acids research · 2022Article
- PICH Supports Embryonic Hematopoiesis by Suppressing a cGAS-STING-Mediated Interferon Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism.PLoS genetics · 2022Article
- Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.Cell reports · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
- A mechanism for Rad53 to couple leading- and lagging-strand DNA synthesis under replication stress in budding yeast.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Hydroxyurea-The Good, the Bad and the Ugly.Genes · 2021Review
- Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity.Science advances · 2020Article
- Review
- High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.Nucleic acids research · 2020Article
- Supraphysiological protection from replication stress does not extend mammalian lifespan.Aging · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.