Evidence map›Paper›PMID 20142431›Full record

ArticleThe Journal of experimental medicine2010

Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4.

Cristian Boboila, Catherine Yan, Duane R Wesemann, Mila Jankovic, Jing H Wang, John Manis, Andre Nussenzweig, Michel Nussenzweig, Frederick W Alt

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 192 citations in OpenAlex.

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52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

9 authors at 6 institutions in 3 countries.

Cristian BoboilaDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Catherine Yan
Duane R Wesemann
Mila Jankovic
Jing H Wang
John Manis
Andre Nussenzweig
Michel Nussenzweig
Frederick W Alt
Beth Israel Deaconess Medical Center · USHoward Hughes Medical Institute · USBrigham and Women's Hospital · USChildren's Hospital · TNNational Cancer Institute · MYRockefeller University · US

Funding

The Role of BCL-6 in Berminal Center FormationP01CA092625 · NCI · DANA-FARBER CANCER INSTITUTE · PI SHIPP, MARGARET A · 2001 to 2011
$32.9M
DNA RepairZIABC010283 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2009 to 2025
$27.0M
Relationship between DNA damage detection and signalingZIABC010959 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2009 to 2025
$27.0M
Transcriptional Regulation of the Allergic ResponseP01AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1999 to 2007
$8.0M
Class Switch Recombination in B LymphocytesR37AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2014 to 2023
$5.4M
SIGNALLING PATHWAYS IN AUTOIMMUNITYR01AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 1994 to 2012
$5.0M
Mechanisms that Regulate Antibody Class Switch Recombination and Somatic HypermutationR37AI077595 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Frederick W. Alt · 2019 to 2026
$4.6M
Molecular Mechanisms of Class Switch RecombinationR01AI077595 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI ALT, FREDERICK W. · 2009 to 2018
$4.3M
Pathobiology of Cancer at the Host and Population LevelT32CA009382 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI YUAN, ZHI-MIN · 1985 to 2012
$2.9M
MOLECULAR BASIS OF IMMUNE FUNCTION IN HEALTH AND DISEASEU19AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1995 to 1998
–
Howard Hughes Medical InstituteNCI NIH HHS CA092625NCI NIH HHS P01 CA092625NCI NIH HHS T32 CA009382NCI NIH HHS T32CA09382-26NIAID NIH HHS AI037526NIAID NIH HHS AI077595NIAID NIH HHS P01 AI031541NIAID NIH HHS R01 AI037526NIAID NIH HHS R01 AI077595NIAID NIH HHS R37 AI037526NIAID NIH HHS R37 AI077595NIAID NIH HHS U19 AI031541
6 · The paper itself

Abstract

The classical nonhomologous end-joining (C-NHEJ) DNA double-strand break (DSB) repair pathway employs the Ku70/80 complex (Ku) for DSB recognition and the XRCC4/DNA ligase 4 (Lig4) complex for ligation. During IgH class switch recombination (CSR) in B lymphocytes, switch (S) region DSBs are joined by C-NHEJ to form junctions either with short microhomologies (MHs; "MH-mediated" joins) or no homologies ("direct" joins). In the absence of XRCC4 or Lig4, substantial CSR occurs via "alternative" end-joining (A-EJ) that generates largely MH-mediated joins. Because upstream C-NHEJ components remain in XRCC4- or Lig4-deficient B cells, residual CSR might be catalyzed by C-NHEJ using a different ligase. To address this, we have assayed for CSR in B cells deficient for Ku70, Ku80, or both Ku70 and Lig4. Ku70- or Ku80-deficient B cells have reduced, but still substantial, CSR. Strikingly, B cells deficient for both Ku plus Lig4 undergo CSR similarly to Ku-deficient B cells, firmly demonstrating that an A-EJ pathway distinct from C-NHEJ can catalyze CSR end-joining. Ku-deficient or Ku- plus Lig4-deficient B cells are also biased toward MH-mediated CSR joins; but, in contrast to XRCC4- or Lig4-deficient B cells, generate substantial numbers of direct CSR joins. Our findings suggest that more than one form of A-EJ can function in CSR.

Indexed as

DNA Breaks, Double-StrandedDNA RepairImmunoglobulin Class SwitchingAnimalsAntigens, NuclearB-LymphocytesDNA-Binding ProteinsDNA Ligase ATPDNA LigasesImmunoglobulinsKu AutoantigenMiceAntigens, NuclearDNA-Binding ProteinsDNA Ligase ATPDNA LigasesImmunoglobulinsKu AutoantigenLIG4 protein, humanXRCC4 protein, humanXrcc6 protein, humanXrcc6 protein, mouse

Identifiers

PMID20142431
PMCPMC2822597
OpenAlexW2138637722

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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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.