Evidence map›Paper›PMID 25154417›Full record

ArticleMolecular and cellular biology2014

Genomic uracil homeostasis during normal B cell maturation and loss of this balance during B cell cancer development.

Sophia Shalhout, Dania Haddad, Angela Sosin, Thomas C Holland, Ayad Al-Katib, Alberto Martin, Ashok S Bhagwat

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Uracil moieties inFEBS open bio · 2018
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
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 2 institutions in 2 countries.

Sophia ShalhoutDepartment of Chemistry, Wayne State University, Detroit, Michigan, USA.
Dania HaddadDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Angela SosinDepartment of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Thomas C HollandDepartment of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Ayad Al-KatibDepartment of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Alberto MartinDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Ashok S BhagwatDepartment of Chemistry, Wayne State University, Detroit, Michigan, USA Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA axb@chem.wayne.edu.
Wayne State University · USUniversity of Toronto · CA

Funding

TRANSCRIPTION--INDUCED MUTATIONSR01GM057200 · NIGMS · WAYNE STATE UNIVERSITY · PI BHAGWAT, ASHOK S · 1998 to 2014
$2.6M
Chemical Development of Fluorescent Labeling Tags for DNA Damaged SitesR03CA153936 · NCI · WAYNE STATE UNIVERSITY · PI ANDREANA, PETER R · 2010 to 2011
$138k
NCI NIH HHS CA153936NCI NIH HHS R03 CA153936NIGMS NIH HHS GM572000NIGMS NIH HHS R01 GM057200
6 · The paper itself

Abstract

Activation-induced deaminase (AID) converts DNA cytosines to uracils in immunoglobulin genes, creating antibody diversification. It also causes mutations and translocations that promote cancer. We examined the interplay between uracil creation by AID and its removal by UNG2 glycosylase in splenocytes undergoing maturation and in B cell cancers. The genomic uracil levels remain unchanged in normal stimulated B cells, demonstrating a balance between uracil generation and removal. In stimulated UNG(-/-) cells, uracil levels increase by 11- to 60-fold during the first 3 days. In wild-type B cells, UNG2 gene expression and enzymatic activity rise and fall with AID levels, suggesting that UNG2 expression is coordinated with uracil creation by AID. Remarkably, a murine lymphoma cell line, several human B cell cancer lines, and human B cell tumors expressing AID at high levels have genomic uracils comparable to those seen with stimulated UNG(-/-)splenocytes. However, cancer cells express UNG2 gene at levels similar to or higher than those seen with peripheral B cells and have nuclear uracil excision activity comparable to that seen with stimulated wild-type B cells. We propose that more uracils are created during B cell cancer development than are removed from the genome but that the uracil creation/excision balance is restored during establishment of cell lines, fixing the genomic uracil load at high levels.

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)AnimalsB-LymphocytesCell Line, TumorCytidine DeaminaseGenomeHumansLipopolysaccharidesLiverLymphoproliferative DisordersMice, Inbred C57BLMice, TransgenicPalatine TonsilSpleenUracilUracil-DNA GlycosidaseAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseLipopolysaccharidesUracilUracil-DNA Glycosidase

Identifiers

PMID25154417
PMCPMC4386458
OpenAlexW2152616082

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.