The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 16 June 2003. doi:10.1084/jem.20030569
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 431K)
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 Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2003/6/1767 $5.00
The Journal of Experimental Medicine, Volume 197, Number 12, 1767-1778

H2AX Is Required for Recombination Between Immunoglobulin Switch Regions but Not for Intra-Switch Region Recombination or Somatic Hypermutation

Bernardo Reina-San-Martin1,2, Simone Difilippantonio3, Leif Hanitsch1, Revati F. Masilamani1, André Nussenzweig3 and Michel C. Nussenzweig1,2

1 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1002
2 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 1002
3 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to M.C. Nussenzweig, The Rockefeller University, RRB Rm. 470, Box 220, Department of Molecular Immunology/HHMI, 1230 York Ave., New York, NY. Phone: 212-327-8067; Fax: 212-327-8370; E-mail: nussen{at}mail.rockefeller.edu

Changes in chromatin structure induced by posttranslational modifications of histones are important regulators of genomic function. Phosphorylation of histone H2AX promotes DNA repair and helps maintain genomic stability. Although B cells lacking H2AX show impaired class switch recombination (CSR), the precise role of H2AX in CSR and somatic hypermutation (SHM) has not been defined. We show that H2AX is not required for SHM, suggesting that the processing of DNA lesions leading to SHM is fundamentally different from CSR. Impaired CSR in H2AX-/- B cells is not due to alterations in switch region transcription, accessibility, or aberrant joining. In the absence of H2AX, short-range intra-switch region recombination proceeds normally while long-range inter-switch region recombination is impaired. Our results suggest a role for H2AX in regulating the higher order chromatin remodeling that facilitates switch region synapsis.

Key Words: class switch recombination • somatic hypermutation • activation-induced cytidine deaminase • H2AX • non-homologous end joining


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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