Evidence map›Paper›PMID 25809478›Full record

ArticleThe Journal of biological chemistry2015

Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation.

Xiangzi Han, Franklin Mayca Pozo, Jacob N Wisotsky, Benlian Wang, James W Jacobberger, Youwei Zhang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 35 citations in OpenAlex.

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  17. [Deguelin inhibits proliferation and regulates the expression of MCM3-CDC45 in MCF-7 and H1299 cells in vitro].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017
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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

6 authors at 1 institution in 1 country.

Xiangzi HanFrom the Departments of Pharmacology and.
Franklin Mayca PozoFrom the Departments of Pharmacology and.
Jacob N WisotskyGenetics and Genome Science.
Benlian WangCenter for Proteomics and Bioinformatics, and.
James W JacobbergerDivision of General Medical Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 Case Comprehensive Cancer Center.
Youwei ZhangFrom the Departments of Pharmacology and Case Comprehensive Cancer Center, Genetics and Genome Science, yxz169@case.edu.
Case Western Reserve University · US

Funding

Spatiotemporal Regulation of Chk1 in Cell Biology, Cancer Etiology and TherapyR01CA163214 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI ZHANG, YOU-WEI · 2012 to 2016
$1.6M
Roles of the Checkpoint Kinase Chk1 in Cancer Biology and TherapyR00CA126173 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI ZHANG, YOU-WEI · 2009 to 2011
$740k
NCI NIH HHS R00 CA126173NCI NIH HHS R01 CA163214
6 · The paper itself

Abstract

Mechanisms controlling DNA replication and replication checkpoint are critical for the maintenance of genome stability and the prevention or treatment of human cancers. Checkpoint kinase 1 (Chk1) is a key effector protein kinase that regulates the DNA damage response and replication checkpoint. The heterohexameric minichromosome maintenance (MCM) complex is the core component of mammalian DNA helicase and has been implicated in replication checkpoint activation. Here we report that Chk1 phosphorylates the MCM3 subunit of the MCM complex at Ser-205 under normal growth conditions. Mutating the Ser-205 of MCM3 to Ala increased the length of DNA replication track and shortened the S phase duration, indicating that Ser-205 phosphorylation negatively controls normal DNA replication. Upon replicative stress treatment, the inhibitory phosphorylation of MCM3 at Ser-205 was reduced, and this reduction was accompanied with the generation of single strand DNA, the key platform for ataxia telangiectasia mutated and Rad3-related (ATR) activation. As a result, the replication checkpoint is activated. Together, these data provide significant insights into the regulation of both normal DNA replication and replication checkpoint activation through the novel phosphorylation of MCM3 by Chk1.

Indexed as

Cell Cycle CheckpointsDNA ReplicationGene Expression RegulationAlanineAtaxia Telangiectasia Mutated ProteinsCell CycleCell Line, TumorCheckpoint Kinase 1ChromatinDNA DamageDNA, Single-StrandedHEK293 CellsHeLa CellsHumansMass SpectrometryMinichromosome Maintenance Complex Component 3AlanineAtaxia Telangiectasia Mutated ProteinsATR protein, humanCheckpoint Kinase 1CHEK1 protein, humanChromatinDNA, Single-StrandedMCM3 protein, humanMinichromosome Maintenance Complex Component 3Protein KinasesSerineCell CycleDNA DamageDNA ReplicationPhosphorylationSignal Transduction

Identifiers

PMID25809478
PMCPMC4424366
OpenAlexW2266724717

What OpenQuestion holds

Textmetadata
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.