Evidence map›Paper›PMID 31381575›Full record

ArticlePLoS genetics2019

Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats.

Xiaoli Li, Xuejiao Jin, Sushma Sharma, Xiaojing Liu, Jiaxin Zhang, Yanling Niu, Jiani Li, Zhen Li, Jingjing Zhang, Qinhong Cao and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Xiaoli LiState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Xuejiao JinState Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Lin'an, Hangzhou, China.
Sushma SharmaDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Xiaojing LiuState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Jiaxin ZhangState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Yanling NiuState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Jiani LiState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Zhen LiState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.ORCID 0000-0002-4798-4161
Jingjing ZhangState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Qinhong CaoState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Wenya HouState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.
Li-Lin DuNational Institute of Biological Sciences, Beijing, China.ORCID 0000-0002-1028-7397
Beidong LiuState Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Lin'an, Hangzhou, China.
Huiqiang LouState Key Laboratory of Agro-Biotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China.ORCID 0000-0003-4465-6186

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. Deleting MCK1 sensitizes dun1Δ to hydroxyurea (HU) reminiscent of mec1Δ or rad53Δ. While Mck1 is downstream of Rad53, it does not participate in the post-translational regulation of RNR as Dun1 does. Mck1 phosphorylates and releases the Crt1 repressor from the promoters of DNA damage-inducible genes as RNR2-4 and HUG1. Hug1, an Rnr2 inhibitor normally silenced, is induced as a counterweight to excessive RNR. When cells suffer a more severe threat, Mck1 inhibits HUG1 transcription. Consistently, only a combined deletion of HUG1 and CRT1, confers a dramatic boost of dNTP levels and the survival of mck1Δdun1Δ or mec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis.

Indexed as

Cell Cycle ProteinsDNA DamageDNA ReplicationGene Expression Regulation, FungalGene Knockout TechniquesGlycogen Synthase Kinase 3HydroxyureaNucleotidesPhosphorylationPromoter Regions, GeneticProtein Serine-Threonine KinasesRepressor ProteinsRibonucleotide ReductasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsS Phase Cell Cycle CheckpointsCell Cycle ProteinsDUN1 protein, S cerevisiaeGlycogen Synthase Kinase 3HydroxyureaMCK1 protein, S cerevisiaeNucleotidesProtein Serine-Threonine KinasesRepressor ProteinsRFX1 protein, S cerevisiaeRibonucleotide ReductasesSaccharomyces cerevisiae Proteins

Identifiers

PMID31381575
PMCPMC6695201

What OpenQuestion holds

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Registered trials

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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.