Evidence map›Paper›PMID 24550291›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

IgH class switching exploits a general property of two DNA breaks to be joined in cis over long chromosomal distances.

Monica Gostissa, Bjoern Schwer, Amelia Chang, Junchao Dong, Robin M Meyers, Gregory T Marecki, Vivian W Choi, Roberto Chiarle, Ali A Zarrin, Frederick W Alt

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Current insights into the mechanism of mammalian immunoglobulin class switch recombination.Critical reviews in biochemistry and molecular biology · 2019
    Review
  4. Review
  5. Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Microbial cell (Graz, Austria) · 2015
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  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

10 authors at 3 institutions in 1 country.

Monica GostissaHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115.
Bjoern Schwer
Amelia Chang
Junchao Dong
Robin M Meyers
Gregory T Marecki
Vivian W Choi
Roberto Chiarle
Ali A Zarrin
Frederick W Alt
Boston Children's Hospital · USHarvard University · USHoward Hughes Medical Institute · US

Funding

The Molecular Function of D-cyclins in T-ALLP01CA109901 · NCI · DANA-FARBER CANCER INSTITUTE · PI YOUNG, RICHARD · 2004 to 2014
$19.6M
Mechanisms that Regulate Antibody Class Switch Recombination and Somatic HypermutationR37AI077595 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Frederick W. Alt · 2019 to 2026
$4.6M
Towards a Mouse Model of Classical Hodgkin's Disease and PTLDR01CA098285 · NCI · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W. · 2003 to 2013
$4.5M
Molecular Mechanisms of Class Switch RecombinationR01AI077595 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI ALT, FREDERICK W. · 2009 to 2018
$4.3M
European Research Council 242965Howard Hughes Medical InstituteNCI NIH HHS P01 CA109901NCI NIH HHS P01CA109901NCI NIH HHS R01 CA098285NCI NIH HHS R01CA098285NIAID NIH HHS R01 AI077595NIAID NIH HHS R01AI077595NIAID NIH HHS R37 AI077595Worldwide Cancer Research 12-0216
6 · The paper itself

Abstract

Antibody class switch recombination (CSR) in B lymphocytes joins two DNA double-strand breaks (DSBs) lying 100-200 kb apart within switch (S) regions in the immunoglobulin heavy-chain locus (IgH). CSR-activated B lymphocytes generate multiple S-region DSBs in the donor Sμ and in a downstream acceptor S region, with a DSB in Sμ being joined to a DSB in the acceptor S region at sufficient frequency to drive CSR in a large fraction of activated B cells. Such frequent joining of widely separated CSR DSBs could be promoted by IgH-specific or B-cell-specific processes or by general aspects of chromosome architecture and DSB repair. Previously, we found that B cells with two yeast I-SceI endonuclease targets in place of Sγ1 undergo I-SceI-dependent class switching from IgM to IgG1 at 5-10% of normal levels. Now, we report that B cells in which Sγ1 is replaced with a 28 I-SceI target array, designed to increase I-SceI DSB frequency, undergo I-SceI-dependent class switching at almost normal levels. High-throughput genome-wide translocation sequencing revealed that I-SceI-generated DSBs introduced in cis at Sμ and Sγ1 sites are joined together in T cells at levels similar to those of B cells. Such high joining levels also occurred between I-SceI-generated DSBs within c-myc and I-SceI- or CRISPR/Cas9-generated DSBs 100 kb downstream within Pvt1 in B cells or fibroblasts, respectively. We suggest that CSR exploits a general propensity of intrachromosomal DSBs separated by several hundred kilobases to be frequently joined together and discuss the relevance of this finding for recurrent interstitial deletions in cancer.

Indexed as

DNA Breaks, Double-StrandedB-LymphocytesDeoxyribonucleases, Type II Site-SpecificDNA PrimersDNA RepairEnzyme-Linked Immunosorbent AssayFlow CytometryImmunoglobulin Class SwitchingImmunoglobulin Heavy ChainsNeoplasmsPolymerase Chain ReactionRecombination, GeneticSaccharomyces cerevisiae ProteinsDeoxyribonucleases, Type II Site-SpecificDNA PrimersImmunoglobulin Heavy ChainsSaccharomyces cerevisiae ProteinsSCEI protein, S cerevisiaedouble-strand break synapsisintrachromosomal joiningtopological domains

Identifiers

PMID24550291
PMCPMC3932927
OpenAlexW2062725457

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.