The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 1 November 2004. doi:10.1084/jem.20041162
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1103-1110
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reina-San-Martin, B.
Right arrow Articles by Nussenzweig, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reina-San-Martin, B.
Right arrow Articles by Nussenzweig, M. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
ATM Is Required for Efficient Recombination between Immunoglobulin Switch Regions

Bernardo Reina-San-Martin1, Hua Tang Chen2, André Nussenzweig2, and Michel C. Nussenzweig1

1 Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
2 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Michel C. Nussenzweig, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8067; Fax: (212) 327-8370; email: nussen{at}mail.rockefeller.edu

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.

Key Words: class switch recombination • somatic hypermutation • activation-induced • cytidine deaminase • ATM • DNA repair

Abbreviations used in this paper: AID, activation-induced cytidine deaminase; ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3 related; CSR, class switch recombination; DNA-PK, DNA-dependent protein kinase; DNA-PKcs, DNA-PK catalytic subunit; DSB, double strand breaks; MRN, complex of Mre11, Rad50, and Nbs1; PIKK, phosphatydil-inositol-3 kinase-like kinase; SHM, somatic hypermutation.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS