Evidence map›Paper›PMID 18974873›Full record

ArticlePLoS genetics2008

Mutation of the zebrafish nucleoporin elys sensitizes tissue progenitors to replication stress.

Gangarao Davuluri, Weilong Gong, Shamila Yusuff, Kristin Lorent, Manimegalai Muthumani, Amy C Dolan, Michael Pack

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing 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

45 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Review
  3. eLife · 2023
    Article
  4. Article
  5. Review
  6. The Journal of biological chemistry · 2020
    Article
  7. Review
  8. Article
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  14. Review
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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

7 authors at 1 institution in 1 country.

Gangarao DavuluriDepartment of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Weilong Gong
Shamila Yusuff
Kristin Lorent
Manimegalai Muthumani
Amy C Dolan
Michael Pack
University of Pennsylvania · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
Exocrine Pancreas &Intestinal Epithelial DevelopmentR01DK061142 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI PACK, MICHAEL A · 2001 to 2005
$2.0M
NIDDK NIH HHS DK61142NIDDK NIH HHS P30 DK050306NIDDK NIH HHS P30 DK50306NIDDK NIH HHS R01 DK061142
6 · The paper itself

Abstract

The recessive lethal mutation flotte lotte (flo) disrupts development of the zebrafish digestive system and other tissues. We show that flo encodes the ortholog of Mel-28/Elys, a highly conserved gene that has been shown to be required for nuclear integrity in worms and nuclear pore complex (NPC) assembly in amphibian and mammalian cells. Maternal elys expression sustains zebrafish flo mutants to larval stages when cells in proliferative tissues that lack nuclear pores undergo cell cycle arrest and apoptosis. p53 mutation rescues apoptosis in the flo retina and optic tectum, but not in the intestine, where the checkpoint kinase Chk2 is activated. Chk2 inhibition and replication stress induced by DNA synthesis inhibitors were lethal to flo larvae. By contrast, flo mutants were not sensitized to agents that cause DNA double strand breaks, thus showing that loss of Elys disrupts responses to selected replication inhibitors. Elys binds Mcm2-7 complexes derived from Xenopus egg extracts. Mutation of elys reduced chromatin binding of Mcm2, but not binding of Mcm3 or Mcm4 in the flo intestine. These in vivo data indicate a role for Elys in Mcm2-chromatin interactions. Furthermore, they support a recently proposed model in which replication origins licensed by excess Mcm2-7 are required for the survival of human cells exposed to replication stress.

Indexed as

ApoptosisDNA ReplicationMutationAmino Acid SequenceAnimalsCell CycleCheckpoint Kinase 2DNA DamageGenes, p53Intestinal MucosaIntestinesMolecular Sequence DataNuclear Pore Complex ProteinsProtein Serine-Threonine KinasesRetinaRNA, MessengerAHCTF1 protein, zebrafishCheckpoint Kinase 2CHEK2 protein, humanNuclear Pore Complex ProteinsProtein Serine-Threonine KinasesRNA, MessengerTranscription FactorsZebrafish Proteins

Identifiers

PMID18974873
PMCPMC2570612
OpenAlexW2053399074

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.