Evidence map›Paper›PMID 22366459›Full record

ArticleJournal of cell science2012

Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation.

Kathleen Klotz-Noack, Debbie McIntosh, Nicholas Schurch, Norman Pratt, J Julian Blow

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

44 citing papers in PubMed, 66 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

5 authors at 2 institutions in 1 country.

Kathleen Klotz-NoackWellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, UK.
Debbie McIntosh
Nicholas Schurch
Norman Pratt
J Julian Blow
University of Dundee · GBNinewells Hospital · GB

Funding

Cancer Research UK 14301Cancer Research UK A7399Cancer Research UK A7999Cancer Research UK C303/A7399Cancer Research UK C303/A7999
6 · The paper itself

Abstract

To prevent re-replication of DNA in a single cell cycle, the licensing of replication origins by Mcm2-7 is prevented during S and G2 phases. Animal cells achieve this by cell-cycle-regulated proteolysis of the essential licensing factor Cdt1 and inhibition of Cdt1 by geminin. Here we investigate the consequences of ablating geminin in synchronised human U2OS cells. Following geminin loss, cells complete an apparently normal S phase, but a proportion arrest at the G2-M boundary. When Cdt1 accumulates in these cells, DNA re-replicates, suggesting that the key role of geminin is to prevent re-licensing in G2. If cell cycle checkpoints are inhibited in cells lacking geminin, cells progress through mitosis and less re-replication occurs. Checkpoint kinases thereby amplify re-replication into an all-or-nothing response by delaying geminin-depleted cells in G2. Deep DNA sequencing revealed no preferential re-replication of specific genomic regions after geminin depletion. This is consistent with the observation that cells in G2 have lost their replication timing information. By contrast, when Cdt1 is overexpressed or is stabilised by the neddylation inhibitor MLN4924, re-replication can occur throughout S phase.

Indexed as

Cell Cycle CheckpointsDNA ReplicationG2 PhaseCell Cycle ProteinsCell Line, TumorCellsGemininHumansMinichromosome Maintenance Complex Component 2Nuclear ProteinsS PhaseCDT1 protein, humanCell Cycle ProteinsGemininGMNN protein, humanMCM2 protein, humanMinichromosome Maintenance Complex Component 2Nuclear Proteins

Identifiers

PMID22366459
PMCPMC3481538
OpenAlexW2097130397

What OpenQuestion holds

Textmetadata
LicenceTDM
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.