Genes and Development

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

GENES & DEVELOPMENT 20:1575-1582, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Research Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reddy, Y. V.R.
Right arrow Articles by Ramsden, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reddy, Y. V.R.
Right arrow Articles by Ramsden, D. A.
Related Content
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

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

Yeturu V.R. Reddy1, Eric J. Perkins2,4 and Dale A. Ramsden1,2,3,5

1 Lineberger Comprehensive Cancer Center, 2 Curriculum in Genetics and Molecular Biology 3 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA

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: DNA repair; V(D)J recombination; double-strand break repair; transposition]

Received March 22, 2006; revised version accepted April 19, 2006.

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

5 Corrresponding author.

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


Add to CiteULike CiteULike   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?

Related Article

Leukemia and lymphoma: a cost of doing business for adaptive immunity
Mark S. Schlissel, Chris R. Kaffer, and John D. Curry
Genes & Dev. 2006 20: 1539-1544. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
C. P. Lu, J. E. Posey, and D. B. Roth
Understanding how the V(D)J recombinase catalyzes transesterification: distinctions between DNA cleavage and transposition
Nucleic Acids Res., May 1, 2008; 36(9): 2864 - 2873.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zhang and P. C. Swanson
V(D)J Recombinase Binding and Cleavage of Cryptic Recombination Signal Sequences Identified from Lymphoid Malignancies
J. Biol. Chem., March 14, 2008; 283(11): 6717 - 6727.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Nishihara, F. Nagawa, T. Imai, and H. Sakano
RAG-Heptamer Interaction in the Synaptic Complex Is a Crucial Biochemical Checkpoint for the 12/23 Recombination Rule
J. Biol. Chem., February 22, 2008; 283(8): 4877 - 4885.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Cui and K. Meek
Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway
PNAS, October 23, 2007; 104(43): 17046 - 17051.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
J. D. Curry, D. Schulz, C. J. Guidos, J. S. Danska, L. Nutter, A. Nussenzweig, and M. S. Schlissel
Chromosomal reinsertion of broken RSS ends during T cell development
J. Exp. Med., October 1, 2007; 204(10): 2293 - 2303.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Mizuuchi, P. A. Rice, S. J. Wardle, D. B. Haniford, and K. Mizuuchi
Control of transposase activity within a transpososome by the configuration of the flanking DNA segment of the transposon
PNAS, September 11, 2007; 104(37): 14622 - 14627.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. Roberts and D. A. Ramsden
Loading of the Nonhomologous End Joining Factor, Ku, on Protein-occluded DNA Ends
J. Biol. Chem., April 6, 2007; 282(14): 10605 - 10613.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Genome Res. Learn. Mem.
Protein Science RNA Genes Dev.
Copyright © 2006 by Cold Spring Harbor Laboratory Press.