ArticleNucleic acids research2010
The ribonucleotide reductase inhibitor, Sml1, is sequentially phosphorylated, ubiquitylated and degraded in response to DNA damage.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- E2 ubiquitin-conjugating enzyme Ubc11 regulates Rst2 protein stability in the fission yeast Schizosaccharomyces pombe.Archives of microbiology · 2025Article
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs.eLife · 2024Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- Article
- Structure and functional determinants of Rad6-Bre1 subunits in the histone H2B ubiquitin-conjugating complex.Nucleic acids research · 2023Article
- Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO.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
- Meiotic DNA breaks activate a streamlined phospho-signaling response that largely avoids protein-level changes.Life science alliance · 2022Article
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Genetic-interaction screens uncover novel biological roles and regulators of transcription factors in fission yeast.G3 (Bethesda, Md.) · 2022Article
- Molecular Biology of Cadmium Toxicity in Saccharomyces cerevisiae.Biological trace element research · 2021Review
- Budding yeast Rad51: a paradigm for how phosphorylation and intrinsic structural disorder regulate homologous recombination and protein homeostasis.Current genetics · 2021Review
- Maximized quantitative phosphoproteomics allows high confidence dissection of the DNA damage signaling network.Scientific reports · 2020Article
- Dun1, a Chk2-related kinase, is the central regulator of securin-separase dynamics during DNA damage signaling.Nucleic acids research · 2020Article
- Sml1 Inhibits the DNA Repair Activity of Rev1 in Saccharomyces cerevisiae during Oxidative Stress.Applied and environmental microbiology · 2020Article
- Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats.PLoS genetics · 2019Article
- DNA damage response activates respiration and thereby enlarges dNTP pools to promote cell survival in budding yeast.The Journal of biological chemistry · 2019Article
- Article
- Rnr1, but not Rnr3, facilitates the sustained telomerase-dependent elongation of telomeres.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of ribonucleotide reductase (RNR) is important for cell survival and genome integrity in the face of genotoxic stress. The Mec1/Rad53/Dun1 DNA damage response kinase cascade exhibits multifaceted controls over RNR activity including the regulation of the RNR inhibitor, Sml1. After DNA damage, Sml1 is degraded leading to the up-regulation of dNTP pools by RNR. Here, we probe the requirements for Sml1 degradation and identify several sites required for in vivo phosphorylation and degradation of Sml1 in response to DNA damage. Further, in a strain containing a mutation in Rnr1, rnr1-W688G, mutation of these sites in Sml1 causes lethality. Degradation of Sml1 is dependent on the 26S proteasome. We also show that degradation of phosphorylated Sml1 is dependent on the E2 ubiquitin-conjugating enzyme, Rad6, the E3 ubiquitin ligase, Ubr2, and the E2/E3-interacting protein, Mub1, which form a complex previously only implicated in the ubiquitylation of Rpn4.
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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.