The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 26 April 2004 doi:10.1084/jem.20040373
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1235-1244
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 475K)
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 McBride, K. M.
Right arrow Articles by Nussenzweig, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McBride, K. M.
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?
Somatic Hypermutation Is Limited by CRM1-dependent Nuclear Export of Activation-induced Deaminase

Kevin M. McBride1, Vasco Barreto1, Almudena R. Ramiro1, Pete Stavropoulos1, and Michel C. Nussenzweig1,2

1 Laboratory of Molecular Immunology and 2 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021

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

Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated in activated B lymphocytes by activation-induced deaminase (AID). AID is thought to make lesions in DNA by deaminating cytidine residues in single-stranded DNA exposed by RNA polymerase during transcription. Although this must occur in the nucleus, AID is found primarily in the cytoplasm. Here we show that AID is actively excluded from the nucleus by an exportin CRM1-dependent pathway. The AID nuclear export signal (NES) is found at the carboxyl terminus of AID in a region that overlaps a sequence required for CSR but not SHM. We find that AID lacking a functional NES causes more hypermutation of a nonphysiologic target gene in transfected fibroblasts. However, the NES does not impact on the rate of mutation of immunoglobulin genes in B lymphocytes, suggesting that the AID NES does not limit AID activity in these cells.

Key Words: somatic hypermutation • activation-induced deaminase • nucleo-cytoplasmic trasnport • B lymphocytes • Ig class switching

Abbreviations used in this paper: AID, activation-induced deaminase; CSR, class switch recombination; GFP, green fluorescent protein; Kan, kanamycin; LMB, leptomycin B; NES, nuclear export signal; NLS, nuclear localization signal; PK, pyruvate kinase; SHM, somatic hypermutation; ssDNA, single-stranded DNA.


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