Evidence map›Paper›PMID 24902048›Full record

ArticlePloS one2014

A high through-put screen for small molecules modulating MCM2 phosphorylation identifies Ryuvidine as an inducer of the DNA damage response.

Jennifer FitzGerald, Laura S Murillo, Gemma O'Brien, Enda O'Connell, Aisling O'Connor, Kevin Wu, Guan-Nan Wang, Michael D Rainey, Alessandro Natoni, Sandra Healy and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

12 authors at 1 institution in 1 country.

Jennifer FitzGeraldCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Laura S MurilloCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland; School of Medicine, National University of Ireland Galway, Galway, Ireland.
Gemma O'BrienCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Enda O'ConnellScreening Core, National Centre for Biomedical Engineering Science, Biosciences, National University of Ireland Galway, Galway, Ireland.
Aisling O'ConnorCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Kevin WuCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Guan-Nan WangCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Michael D RaineyCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Alessandro NatoniCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland; School of Medicine, National University of Ireland Galway, Galway, Ireland.
Sandra HealyCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Michael O'DwyerSchool of Medicine, National University of Ireland Galway, Galway, Ireland.
Corrado SantocanaleCentre for Chromosome Biology and National Centre for Biomedical Engineering Science, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Ollscoil na Gaillimhe – University of Galway · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA replication is an essential process for cell division and as such it is a process that is directly targeted by several anticancer drugs. CDC7 plays an essential role in the activation of replication origins and has recently been proposed as a novel target for drug discovery. The MCM DNA helicase complex (MCM2-7) is a key target of the CDC7 kinase, and MCM phosphorylation status at specific sites is a reliable biomarker of CDC7 cellular activity. In this work we describe a cell-based assay that utilizes the "In Cell Western Technique" (ICW) to identify compounds that affect cellular CDC7 activity. By screening a library of approved drugs and kinase inhibitors we found several compounds that can affect CDC7-dependent phosphorylation of MCM2 in HeLa cells. Among these, Mitoxantrone, a topoisomerase inhibitor, and Ryuvidine, previously described as a CDK4 inhibitor, cause a reduction in phosphorylated MCM2 levels and a sudden blockade of DNA synthesis that is accompanied by an ATM-dependent checkpoint response. This study sheds light on the previously observed cytotoxity of Ryuvidine, strongly suggesting that it is related to its effect of causing DNA damage.

Indexed as

Drug DiscoveryCell Cycle ProteinsDNA DamageDNA ReplicationEnzyme ActivationEnzyme InhibitorsHeLa CellsHigh-Throughput Screening AssaysHumansMinichromosome Maintenance Complex Component 2PhosphorylationProtein Serine-Threonine KinasesReproducibility of ResultsSmall Molecule LibrariesCDC7 protein, humanCell Cycle ProteinsEnzyme InhibitorsMinichromosome Maintenance Complex Component 2Protein Serine-Threonine KinasesSmall Molecule Libraries

Identifiers

PMID24902048
PMCPMC4047068
OpenAlexW1997924988

What OpenQuestion holds

Textmetadata
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.