Evidence map›Paper›PMID 24067972›Full record

ArticleJournal of virology2013

Replication stress and mitotic dysfunction in cells expressing simian virus 40 large T antigen.

Liang Hu, Harilaos Filippakis, Haomin Huang, Timothy J Yen, Ole V Gjoerup

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Immortalization of primary sheep embryo kidney cells.In vitro cellular & developmental biology. Animal · 2021
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
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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 4 institutions in 2 countries.

Liang HuMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
Harilaos Filippakis
Haomin Huang
Timothy J Yen
Ole V Gjoerup
Fox Chase Cancer Center · USCentral South University · CNMolecular Oncology (United States) · USTufts Medical Center · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
Role of Bub1 in SV40 large T antigen mediated transformation and replicationR01AI078926 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GJOERUP, OLE · 2008 to 2011
$1.5M
Chemosensitization of Pancreatic Cancer Cells by Curcumin and Vitamin D ReceptorR21CA169706 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI YEN, TIMOTHY · 2013 to 2014
$420k
NCI NIH HHS CA06927NCI NIH HHS CA169706NCI NIH HHS P30 CA006927NCI NIH HHS R21 CA169706NIAID NIH HHS R01 AI078926NIAID NIH HHS R01AI078926
6 · The paper itself

Abstract

We previously demonstrated that simian virus 40 (SV40) large T antigen (LT) binds to the Bub1 kinase, a key regulator of the spindle checkpoint and chromosome segregation. Bub1 mutations or altered expression patterns are linked to chromosome missegregation and are considered to be a driving force in some human cancers. Here we report that LT, dependent on Bub1 binding, causes micronuclei, lagging chromatin, and anaphase bridges, which are hallmarks of chromosomal instability (CIN) and Bub1 insufficiency. Using time-lapse microscopy, we demonstrate that LT imposes a Bub1 binding-dependent delay in the metaphase-to-anaphase transition. Kinetochore fibers reveal that LT, via Bub1 binding, causes aberrant kinetochore (KT)-microtubule (MT) attachments and a shortened interkinetochore distance, consistent with a lack of tension. Previously, we showed that LT also induces the DNA damage response (DDR) via Bub1 binding. Using inducible LT cell lines, we show that an activated DDR was observed before the appearance of anaphase bridges and micronuclei. Furthermore, LT induction in serum-starved cells demonstrated γ-H2AX accumulation in cells that had not yet entered mitosis. Thus, DDR activation can occur independently of chromosome segregation defects. Replication stress pathways may be responsible, because signatures of replication stress were observed, which were attenuated by exogenous supplementation with nucleosides. Our observations allow us to propose a model that explains and integrates the diverse manifestations of genomic instability induced by LT.

Indexed as

DNA ReplicationAnaphaseAntigens, Viral, TumorChromatinChromosomal InstabilityDNA DamageHumansKinetochoresMitosisPolyomavirus InfectionsProtein Serine-Threonine KinasesSimian virus 40Tumor Virus InfectionsAntigens, Viral, TumorBUB1 protein, humanChromatinProtein Serine-Threonine Kinases

Identifiers

PMID24067972
PMCPMC3838287
OpenAlexW2152747396

What OpenQuestion holds

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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.