Evidence map›Paper›PMID 22615128›Full record

ArticleThe Journal of experimental medicine2012

DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions.

Huseyin Saribasak, Robert W Maul, Zheng Cao, William W Yang, Dominik Schenten, Sven Kracker, Patricia J Gearhart

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Tandem Substitutions in Somatic Hypermutation.Frontiers in immunology · 2021
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
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  12. Article
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  14. Review
  15. Article
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  17. APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. Article
  19. Review
  20. 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 3 institutions in 1 country.

Huseyin SaribasakLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Robert W Maul
Zheng Cao
William W Yang
Dominik Schenten
Sven Kracker
Patricia J Gearhart
National Institute on Aging · USHarvard University · USNational Institutes of Health · US

Funding

Protein Interactions in Antibody DiversityZIAAG000732 · NIA · NATIONAL INSTITUTE ON AGING · PI GEARHART, PATRICIA J · 2009 to 2025
$10.7M
Intramural NIH HHS
6 · The paper itself

Abstract

Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although DNA polymerase (pol) η is the major low-fidelity polymerase, other DNA polymerases may also contribute. Existing data are contradictory as to whether pol ζ is involved. We reasoned that the presence of pol η may mask the contribution of pol ζ, and therefore we generated mice deficient for pol η and heterozygous for pol ζ. The frequency and spectra of hypermutation was unaltered between Polζ(+/-) Polη(-/-) and Polζ(+/+) Polη(-/-) clones. However, there was a decrease in tandem double-base substitutions in Polζ(+/-) Polη(-/-) cells compared with Polζ(+/+) Polη(-/-) cells, suggesting that pol ζ generates tandem mutations. Contiguous mutations are consistent with the biochemical property of pol ζ to extend a mismatch with a second mutation. The presence of this unique signature implies that pol ζ contributes to mutational synthesis in vivo. Additionally, data on tandem mutations from wild type, Polζ(+/-), Polζ(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol ζ may function in the MSH2-MSH6 pathway.

Indexed as

MutationAnimalsCell DivisionDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA Mismatch RepairHeterozygoteImmunoglobulin Variable RegionMiceMice, Mutant StrainsMutS Homolog 2 ProteinSomatic Hypermutation, ImmunoglobulinUracil-DNA GlycosidaseY-Family DNA PolymerasesDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA polymerase zetaImmunoglobulin Variable RegionMsh2 protein, mouseMsh6 protein, mouseMutS Homolog 2 ProteinRad30 proteinREV3L protein, mouseUracil-DNA GlycosidaseY-Family DNA Polymerases

Identifiers

PMID22615128
PMCPMC3371727
OpenAlexW2147967811

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.