Evidence map›Paper›PMID 23236290›Full record

ArticlePLoS genetics2012

A yeast GSK-3 kinase Mck1 promotes Cdc6 degradation to inhibit DNA re-replication.

Amy E Ikui, Valentina Rossio, Lea Schroeder, Satoshi Yoshida

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
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

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
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  10. PP2AJournal of cell science · 2020
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  16. A new cell cycle checkpoint that senses plasma membrane/cell wall damage in budding yeast.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017
    Review
  17. Article
  18. Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Amy E IkuiDepartment of Biology, Brooklyn College, The City University of New York, Brooklyn, New York, United States of America. AIkui@brooklyn.cuny.edu
Valentina Rossio
Lea Schroeder
Satoshi Yoshida
Brandeis University · USBrooklyn College · US

Funding

A novel function of Orc6 during mitosis in S. cerevisiaeSC2GM092786 · NIGMS · BROOKLYN COLLEGE · PI IKUI, AMY E · 2010 to 2012
$468k
NIGMS NIH HHS 5SC2GM092786NIGMS NIH HHS SC2 GM092786
6 · The paper itself

Abstract

Cdc6p is an essential component of the pre-replicative complex (pre-RC), which binds to DNA replication origins to promote initiation of DNA replication. Only once per cell cycle does DNA replication take place. After initiation, the pre-RC components are disassembled in order to prevent re-replication. It has been shown that the N-terminal region of Cdc6p is targeted for degradation after phosphorylation by Cyclin Dependent Kinase (CDK). Here we show that Mck1p, a yeast homologue of GSK-3 kinase, is also required for Cdc6 degradation through a distinct mechanism. Cdc6 is an unstable protein and is accumulated in the nucleus only during G1 and early S-phase in wild-type cells. In mck1 deletion cells, CDC6p is stabilized and accumulates in the nucleus even in late S phase and mitosis. Overexpression of Mck1p induces rapid Cdc6p degradation in a manner dependent on Threonine-368, a GSK-3 phosphorylation consensus site, and SCF(CDC4). We show evidence that Mck1p-dependent degradation of Cdc6 is required for prevention of DNA re-replication. Loss of Mck1 activity results in synthetic lethality with other pre-RC mutants previously implicated in re-replication control, and these double mutant strains over-replicate DNA within a single cell cycle. These results suggest that a GSK3 family protein plays an unexpected role in preventing DNA over-replication through Cdc6 degradation in Saccharomyces cerevisiae. We propose that both CDK and Mck1 kinases are required for Cdc6 degradation to ensure a tight control of DNA replication.

Indexed as

Cell Cycle ProteinsCyclin-Dependent KinasesDNA ReplicationGlycogen Synthase Kinase 3Saccharomyces cerevisiae ProteinsCell NucleusMitosisProteolysisSaccharomyces cerevisiaeS PhaseCDC6 protein, S cerevisiaeCell Cycle ProteinsCyclin-Dependent KinasesGlycogen Synthase Kinase 3MCK1 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID23236290
PMCPMC3516531
OpenAlexW2018333214

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.