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PMID: 15520243 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

ATM is required for efficient recombination between immunoglobulin switch regions.

The Journal of experimental medicine ·Vol. 200 ·No. 9 ·2004-11-01 ·Pages 1103-10

Reina-San-Martin B, Chen HT, Nussenzweig A, Nussenzweig MC

Abstract

Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the signaling pathways that lead to cell cycle checkpoints and DNA double strand break repair. In the absence of ATM, humans and mice show a primary immunodeficiency that includes low serum antibody titers, but the role of ATM in antigen-driven immunoglobulin gene diversification has not been defined. Here, we show that although ATM is dispensable for somatic hypermutation, it is required for efficient class switch recombination (CSR). The defect in CSR is not due to alterations in switch region transcription, accessibility, DNA damage checkpoint protein recruitment, or short-range intra-switch region recombination. Only long-range inter-switch recombination is defective, indicating an unexpected role for ATM in switch region synapsis during CSR.

MeSH Terms
Animals Ataxia Telangiectasia Mutated Proteins B-Lymphocytes/immunology Blotting, Southern Cell Cycle Proteins DNA Mutational Analysis DNA-Binding Proteins Enzyme-Linked Immunosorbent Assay Humans Immunoglobulin Class Switching/genetics In Situ Hybridization, Fluorescence Mice Mice, Inbred Strains Protein Serine-Threonine Kinases/genetics,metabolism Recombination, Genetic/genetics Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic/immunology Tumor Suppressor Proteins
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Tumor Suppressor Proteins ATM protein, human Ataxia Telangiectasia Mutated Proteins Atm protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Reina-San-Martin Bernardo
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA.
Chen Hua Tang
Nussenzweig André
Nussenzweig Michel C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20041162
Published
2004-11-01
Pages
1103-10
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2211855
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20041162 PMC Full Text View journal details
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