Genomic instability due to V(D)J recombination-associated transposition

  1. Yeturu V.R. Reddy1,
  2. Eric J. Perkins2,4, and
  3. Ramsden1,2,3,5
  1. 1 Lineberger Comprehensive Cancer Center,
  2. 2 Curriculum in Genetics and Molecular Biology
  3. 3 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA

Abstract

The first step in assembling immunoglobulin and T-cell receptors by V(D)J recombination has similarities to transposon excision. The excised transposon-like element then integrates into DNA targets at random in vitro, but whether this activity significantly threatens the genomic integrity of its host has been unclear. Here, we recover examples where the putative transposon associated with V(D)J recombination integrated into the genome of a pre-B-cell line. Transposition accounted for a surprisingly high proportion (one-third) of integrations, while most of the remaining events had parallels to other aberrant V(D)J recombination pathways linked to oncogenic translocation. In total, transposition occurred approximately once every 50,000 V(D)J recombinations. Transposition may thus contribute significantly to genomic instability.

Keywords

Footnotes

  • 4

    4 Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Biolabs Room 2025, Cambridge, MA 02453, USA.

  • 5

    5 Corrresponding author.

    5 EMAIL dale_ramsden{at}med.unc.edu; FAX (919) 966-3015.

  • Supplemental material is available at http://www.genesdev.org.

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1432706

    • Received March 22, 2006.
    • Accepted April 19, 2006.

Related Article

| Table of Contents

G&D Most Read

View all ...

Life Science Alliance