Evidence map›Paper›PMID 15051760›Full record

ArticleThe Journal of experimental medicine2004

Absence of DNA polymerase eta reveals targeting of C mutations on the nontranscribed strand in immunoglobulin switch regions.

Xianmin Zeng, George A Negrete, Cynthia Kasmer, William W Yang, Patricia J Gearhart

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Mechanism of somatic hypermutation at the WA motif by human DNA polymerase η.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. AID and somatic hypermutation.Advances in immunology · 2010
    Review
  15. Article
  16. Article
  17. Article
  18. Hijacked DNA repair proteins and unchained DNA polymerases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009
    Review
  19. Article
  20. Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression.Proceedings of the National Academy of Sciences of the United States of America · 2008
    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

5 authors at 2 institutions in 1 country.

Xianmin ZengLaboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
George A Negrete
Cynthia Kasmer
William W Yang
Patricia J Gearhart
National Institutes of Health · USNational Institute on Aging · US

Funding

Protein Interactions in Antibody DiversityZIAAG000732 · NIA · NATIONAL INSTITUTE ON AGING · PI GEARHART, PATRICIA J · 2009 to 2025
$10.7M
Protein Interactions in Antibody DiversityZ01AG000732 · NIA · NATIONAL INSTITUTE ON AGING · PI GEARHART, PATRICIA J · 1996 to 2008
$974k
6 · The paper itself

Abstract

Activation-induced cytosine deaminase preferentially deaminates C in DNA on the nontranscribed strand in vitro, which theoretically should produce a large increase in mutations of C during hypermutation of immunoglobulin genes. However, a bias for C mutations has not been observed among the mutations in variable genes. Therefore, we examined mutations in the mu and gamma switch regions, which can form stable secondary structures, to look for C mutations. To further simplify the pattern, mutations were studied in the absence of DNA polymerase (pol) eta, which may produce substitutions of nucleotides downstream of C. DNA from lymphocytes of patients with xeroderma pigmentosum variant (XP-V) disease, whose polymerase eta is defective, had the same frequency of switching to all four gamma isotypes and hypermutation in mu-gamma switch sites (0.5% mutations per basepair) as control subjects. There were fewer mutations of A and T bases in the XP-V clones, similar to variable gene mutations from these patients, which confirms that polymerase eta produces substitutions opposite A and T. Most importantly, the absence of polymerase eta revealed an increase in C mutations on the nontranscribed strand. This data shows for the first time that C is preferentially mutated in vivo and pol eta generates hypermutation in the mu and gamma switch regions.

Indexed as

Immunoglobulin Switch RegionMutationAICDA (Activation-Induced Cytidine Deaminase)Base SequenceCytidine DeaminaseCytosine DeaminaseDNADNA-Directed DNA PolymeraseHumansImmunoglobulin gamma-ChainsImmunoglobulin mu-ChainsModels, GeneticMolecular Sequence DataSomatic Hypermutation, ImmunoglobulinTranscription, GeneticXeroderma PigmentosumAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseCytosine DeaminaseDNADNA-Directed DNA PolymeraseImmunoglobulin gamma-ChainsImmunoglobulin mu-ChainsRad30 proteinY-Family DNA Polymerases

Identifiers

PMID15051760
PMCPMC2211872
OpenAlexW2018861546

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.