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Science 15 March 1996:
Vol. 271. no. 5255, pp. 1592 - 1594
DOI: 10.1126/science.271.5255.1592
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Reports

Similarities Between Initiation of V(D)J Recombination and Retroviral Integration

Dik C. van Gent, Kiyoshi Mizuuchi, Martin Gellert *

In the first step of V(D)J recombination, the RAG1 and RAG2 proteins cleave DNA between a signal sequence and the adjacent coding sequence, generating a blunt signal end and a coding end with a closed hairpin structure. These hairpins are intermediates leading to the formation of assembled antigen receptor genes. It is shown here that the hairpins are formed by a chemical mechanism of direct trans-esterification, very similar to the early steps of transpositional recombination and retroviral integration. A minor variation in the reaction is sufficient to divert the process from transposition to hairpin formation.

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0540, USA.
* To whom correspondence should be addressed.


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J. Immunol. 162, 903-910
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V(D)J Recombination: Links to Transposition and Double-strand Break Repair.
M. GELLERT, J.E. HESSE, K. HIOM, M. MELEK, M. MODESTI, T.T. PAULL, D.A. RAMSDEN, and D.C. VAN GENT (1999)
Cold Spring Harb Symp Quant Biol 64, 161-168
   Abstract »    PDF »
The RAG-HMG1 Complex Enforces the 12/23 Rule of V(D)J Recombination Specifically at the Double-Hairpin Formation Step.
R. B. West and M. R. Lieber (1998)
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   Abstract »    Full Text »
Pathological and Physiological Double-Strand Breaks : Roles in Cancer, Aging, and the Immune System.
M. R. Lieber (1998)
Am. J. Pathol. 153, 1323-1332
   Abstract »    Full Text »    PDF »
A Preferred Target DNA Structure for Retroviral Integrase in Vitro.
R. A. Katz, K. Gravuer, and A. M. Skalka (1998)
J. Biol. Chem. 273, 24190-24195
   Abstract »    Full Text »    PDF »
Distinct Roles of RAG1 and RAG2 in Binding the V(D)J Recombination Signal Sequences.
Y. Akamatsu and M. A. Oettinger (1998)
Mol. Cell. Biol. 18, 4670-4678
   Abstract »    Full Text »
Functional Analysis of Coordinated Cleavage in V(D)J Recombination.
D. R. Kim and M. A. Oettinger (1998)
Mol. Cell. Biol. 18, 4679-4688
   Abstract »    Full Text »
Extensive, Nonrandom Diversity of Excision Footprints Generated by Ds-Like Transposon Ascot-1 Suggests New Parallels with V(D)J Recombination.
V. Colot, V. Haedens, and J.-L. Rossignol (1998)
Mol. Cell. Biol. 18, 4337-4346
   Abstract »    Full Text »
The Effect of Me2+ Cofactors at the Initial Stages of V(D)J Recombination.
S. Santagata, V. Aidinis, and E. Spanopoulou (1998)
J. Biol. Chem. 273, 16325-16331
   Abstract »    Full Text »    PDF »
Functional Characterization of the Tn5 Transposase by Limited Proteolysis.
L. A. M. Braam and W. S. Reznikoff (1998)
J. Biol. Chem. 273, 10908-10913
   Abstract »    Full Text »    PDF »
Rejoining of DNA by the RAG1 and RAG2 Proteins.
M. Melek, M. Gellert, and D. C. van Gent (1998)
Science 280, 301-303
   Abstract »    Full Text »
Structure of Nonhairpin Coding-End DNA Breaks in Cells Undergoing V(D)J Recombination.
M. S. Schlissel (1998)
Mol. Cell. Biol. 18, 2029-2037
   Abstract »    Full Text »
Drosophila P-element transposase is a novel site-specific endonuclease.
E. L. Beall and D. C. Rio (1997)
Genes & Dev. 11, 2137-2151
   Abstract »    Full Text »    PDF »
V(D)J Recombination: Modulation of RAG1 and RAG2 Cleavage Activity on 12/23 Substrates by Whole Cell Extract and DNA-bending Proteins.
D. J. Sawchuk, F. Weis-Garcia, S. Malik, E. Besmer, M. Bustin, M. C. Nussenzweig, and P. Cortes (1997)
J. Exp. Med. 185, 2025-2032
   Abstract »    Full Text »    PDF »
Disruption of the terminal base pairs of retroviral DNA during integration..
B P Scottoline, S Chow, V Ellison, and P O Brown (1997)
Genes & Dev. 11, 371-382
   Abstract »    PDF »
Retroviral Integrase, Putting the Pieces Together.
M. D. Andrake and A. M. Skalka (1996)
J. Biol. Chem. 271, 19633-19636
   Full Text »    PDF »
Degradation of HIV-1 Integrase by the N-end Rule Pathway.
L. C. F. Mulder and M. A. Muesing (2000)
J. Biol. Chem. 275, 29749-29753
   Abstract »    Full Text »    PDF »
Identification of Two Topologically Independent Domains in RAG1 and Their Role in Macromolecular Interactions Relevant to V(D)J Recombination.
J. L. Arbuckle, L. J. Fauss, R. Simpson, L. M. Ptaszek, and K. K. Rodgers (2001)
J. Biol. Chem. 276, 37093-37101
   Abstract »    Full Text »    PDF »
Effect of HIV integrase inhibitors on the RAG1/2 recombinase.
M. Melek, J. M. Jones, M. H. O'Dea, G. Pais, T. R. Burke Jr., Y. Pommier, N. Neamati, and M. Gellert (2002)
PNAS 99, 134-137
   Abstract »    Full Text »    PDF »
Intermediates in V(D)J recombination: A stable RAG1/2 complex sequesters cleaved RSS ends.
J. M. Jones and M. Gellert (2001)
PNAS 98, 12926-12931
   Abstract »    Full Text »    PDF »


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