ArticleThe EMBO journal2001
The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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Who cites it
173 citing papers in PubMed, 286 citations in OpenAlex.
- Slx4 and Fun30/SMARCAD1 coordinate S-phase checkpoint regulation and replication fork protection in response to Top1-DNA crosslinks.Nucleic acids research · 2026Article
- Structural insights into the Bre1-Lge1 and RNF20/RNF40-WAC interactions critical for H2B ubiquitination.Nucleic acids research · 2026Article
- The yeast checkpoint kinase Mec1p functions in transcription termination by facilitating recruitment of Pcf11p and regulating the torpedo exonuclease Rat1p.Scientific reports · 2025Article
- The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells.Molecular cell · 2025Article
- DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025Review
- Article
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- Decoupled transcript and protein concentrations ensure histone homeostasis in different nutrients.The EMBO journal · 2024Article
- Multi-step control of homologous recombination via Mec1/ATR suppresses chromosomal rearrangements.The EMBO journal · 2024Article
- Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers.G3 (Bethesda, Md.) · 2024Article
- Physical interactions between specifically regulated subpopulations of the MCM and RNR complexes prevent genetic instability.PLoS genetics · 2024Article
- Dynamics of DNA damage-induced nuclear inclusions are regulated by SUMOylation of Btn2.Nature communications · 2024Article
- Hydroxyurea and inactivation of checkpoint kinase MEC1 inhibit transcription termination and pre-mRNA cleavage at polyadenylation sites in budding yeast.Scientific reports · 2023Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- Tolerance to replication stress requires Dun1p kinase and activation of the electron transport chain.Biochimica et biophysica acta. Molecular cell research · 2023Article
- Persistent Acetylation of Histone H3 Lysine 56 Compromises the Activity of DNA Replication Origins.Molecular and cellular biology · 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
- Review
- CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism.PLoS genetics · 2022Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The evolutionarily conserved protein kinases Mec1 and Rad53 are required for checkpoint response and growth. Here we show that their role in growth is to remove the ribonucleotide reductase inhibitor Sml1 to ensure DNA replication. Sml1 protein levels fluctuate during the cell cycle, being lowest during S phase. The disappearance of Sml1 protein in S phase is due to post-transcriptional regulation and is associated with protein phosphorylation. Both phosphorylation and diminution of Sml1 require MEC1 and RAD53. More over, failure to remove Sml1 in mec1 and rad53 mutants results in incomplete DNA replication, defective mitochondrial DNA propagation, decreased dNTP levels and cell death. Interestingly, similar regulation of Sml1 also occurs after DNA damage. In this case, the regulation requires MEC1 and RAD53, as well as other checkpoint genes. Therefore, Sml1 is a new target of the DNA damage checkpoint and its removal is a conserved function of Mec1 and Rad53 during growth and after damage.
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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.