ArticlePLoS genetics2017
Rnr1, but not Rnr3, facilitates the sustained telomerase-dependent elongation of telomeres.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers.Signal transduction and targeted therapy · 2026Article
- Telomeres: Dysfunction, Maintenance, Aging and Cancer.Aging and disease · 2023Review
- Article
- Deletion of MEC1 suppresses the replicative senescence of the cdc13-2 mutant in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2023Article
- SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Thymidine nucleotide metabolism controls human telomere length.Nature genetics · 2023Article
- Swc4 positively regulates telomere length independently of its roles in NuA4 and SWR1 complexes.Nucleic acids research · 2020Article
- RNases H1 and H2: guardians of the stability of the nuclear genome when supply of dNTPs is limiting for DNA synthesis.Current genetics · 2020Review
- High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.Nucleic acids research · 2020Article
- Inactivation of folylpolyglutamate synthetase Met7 results in genome instability driven by an increased dUTP/dTTP ratio.Nucleic acids research · 2020Article
- Genomic Instability and Cellular Senescence: Lessons From the Budding Yeast.Frontiers in cell and developmental biology · 2020Review
- Tel1 Activation by the MRX Complex Is Sufficient for Telomere Length Regulation but Not for the DNA Damage Response inGenetics · 2019Article
- A genetic screen pinpoints ribonucleotide reductase residues that sustain dNTP homeostasis and specifies a highly mutagenic type of dNTP imbalance.Nucleic acids research · 2019Article
- Rnr1's role in telomere elongation cannot be replaced by Rnr3: a role beyond dNTPs?Current genetics · 2018Review
- Histone depletion prevents telomere fusions in pre-senescent cells.PLoS genetics · 2018Article
- Clinicopathological and Prognostic Values of Telomerase Reverse Transcriptase (Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribonucleotide reductase (RNR) provides the precursors for the generation of dNTPs, which are required for DNA synthesis and repair. Here, we investigated the function of the major RNR subunits Rnr1 and Rnr3 in telomere elongation in budding yeast. We show that Rnr1 is essential for the sustained elongation of short telomeres by telomerase. In the absence of Rnr1, cells harbor very short, but functional, telomeres, which cannot become elongated by increased telomerase activity or by tethering of telomerase to telomeres. Furthermore, we demonstrate that Rnr1 function is critical to prevent an early onset of replicative senescence and premature survivor formation in telomerase-negative cells but dispensable for telomere elongation by Homology-Directed-Repair. Our results suggest that telomerase has a "basal activity" mode that is sufficient to compensate for the "end-replication-problem" and does not require the presence of Rnr1 and a different "sustained activity" mode necessary for the elongation of short telomeres, which requires an upregulation of dNTP levels and dGTP ratios specifically through Rnr1 function. By analyzing telomere length and dNTP levels in different mutants showing changes in RNR complex composition and activity we provide evidence that the Mec1ATR checkpoint protein promotes telomere elongation by increasing both dNTP levels and dGTP ratios through Rnr1 upregulation in a mechanism that cannot be replaced by its homolog Rnr3.
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