Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 20 November 1987:
Vol. 238. no. 4830, pp. 1134 - 1138
DOI: 10.1126/science.3120312
Prev | Table of Contents | Next

Articles

Science, Vol 238, Issue 4830, 1134-1138
Copyright © 1987 by American Association for the Advancement of Science

articles

Two pairs of recombination signals are sufficient to cause immunoglobulin V-(D)-J joining

S Akira, K Okazaki, and H Sakano

Department of Microbiology and Immunology, University of California, Berkeley 94720.

The minimum sequence requirements for antigen receptor V-(D)-J joining were studied by constructing recombination-substrates containing synthetic recombination signals and introducing them into a recombination-competent pre-B cell line. Two sets of heptamer (CACTGTG) and nonamer (GGTTTTTGT) sequences were shown to be sufficient to cause the V-(D)-J joining, if the 12- and 23-base pair spacer rule is satisfied. A point mutation in the heptamer sequence, or a change in the combination of the two spacer lengths, drastically reduced the recombination.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Impact of a hypomorphic Artemis disease allele on lymphocyte development, DNA end processing, and genome stability.
Y. Huang, W. Giblin, M. Kubec, G. Westfield, J. St. Charles, L. Chadde, S. Kraftson, and J. Sekiguchi (2009)
J. Exp. Med. 206, 893-908
   Abstract »    Full Text »    PDF »
Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers.
S. Das, N. Nikolaidis, J. Klein, and M. Nei (2008)
PNAS 105, 16647-16652
   Abstract »    Full Text »    PDF »
RAG-Heptamer Interaction in the Synaptic Complex Is a Crucial Biochemical Checkpoint for the 12/23 Recombination Rule.
T. Nishihara, F. Nagawa, T. Imai, and H. Sakano (2008)
J. Biol. Chem. 283, 4877-4885
   Abstract »    Full Text »    PDF »
Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombination.
H. Lu, K. Schwarz, and M. R. Lieber (2007)
Nucleic Acids Res. 35, 6917-6923
   Abstract »    Full Text »    PDF »
Paucity of V-D-D-J Rearrangements and VH Replacement Events in Lupus Prone and Nonautoimmune TdT-/- and TdT+/+ Mice.
L. C. Watson, C. S. Moffatt-Blue, R. Z. McDonald, E. Kompfner, D. Ait-Azzouzene, D. Nemazee, A. N. Theofilopoulos, D. H. Kono, and A. J. Feeney (2006)
J. Immunol. 177, 1120-1128
   Abstract »    Full Text »    PDF »
Joining Mutants of RAG1 and RAG2 that Demonstrate Impaired Interactions with the Coding-end DNA.
F. Nagawa, S. Hirose, H. Nishizumi, T. Nishihara, and H. Sakano (2004)
J. Biol. Chem. 279, 38360-38368
   Abstract »    Full Text »    PDF »
V(D)J Recombination Frequencies Can Be Profoundly Affected by Changes in the Spacer Sequence.
A. Montalbano, K. M. Ogwaro, A. Tang, A. G. W. Matthews, M. Larijani, M. A. Oettinger, and A. J. Feeney (2003)
J. Immunol. 171, 5296-5304
   Abstract »    Full Text »    PDF »
Prospective Estimation of Recombination Signal Efficiency and Identification of Functional Cryptic Signals in the Genome by Statistical Modeling.
L. G. Cowell, M. Davila, K. Yang, T. B. Kepler, and G. Kelsoe (2003)
J. Exp. Med. 197, 207-220
   Abstract »    Full Text »    PDF »
Footprint Analysis of Recombination Signal Sequences in the 12/23 Synaptic Complex of V(D)J Recombination.
F. Nagawa, M. Kodama, T. Nishihara, K.-i. Ishiguro, and H. Sakano (2002)
Mol. Cell. Biol. 22, 7217-7225
   Abstract »    Full Text »    PDF »
The Cleavage Efficiency of the Human Immunoglobulin Heavy Chain VH Elements by the RAG Complex. IMPLICATIONS FOR THE IMMUNE REPERTOIRE.
K. Yu, A. Taghva, and M. R. Lieber (2002)
J. Biol. Chem. 277, 5040-5046
   Abstract »    Full Text »    PDF »
V(D)J-mediated Translocations in Lymphoid Neoplasms: A Functional Assessment of Genomic Instability by Cryptic Sites.
R. Marculescu, T. Le, P. Simon, U. Jaeger, and B. Nadel (2002)
J. Exp. Med. 195, 85-98
   Abstract »    Full Text »    PDF »
Unequal VH Gene Rearrangement Frequency Within the Large VH7183 Gene Family Is Not Due to Recombination Signal Sequence Variation, and Mapping of the Genes Shows a Bias of Rearrangement Based on Chromosomal Location.
G. S. Williams, A. Martinez, A. Montalbano, A. Tang, A. Mauhar, K. M. Ogwaro, D. Merz, C. Chevillard, R. Riblet, and A. J. Feeney (2001)
J. Immunol. 167, 257-263
   Abstract »    Full Text »    PDF »
Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of JH-proximal variable gene segments.
F. Y. Mortuza, I. M. Moreira, M. Papaioannou, P. Gameiro, L. A. Coyle, C. S. Gricks, P. Amlot, H. G. Prentice, A. Madrigal, A. V. Hoffbrand, et al. (2001)
Blood 97, 2716-2726
   Abstract »    Full Text »    PDF »
N-terminal truncated human RAG1 proteins can direct T-cell receptor but not immunoglobulin gene rearrangements.
J. G. Noordzij, N. S. Verkaik, N. G. Hartwig, R. de Groot, D. C. van Gent, and J. J. M. van Dongen (2000)
Blood 96, 203-209
   Abstract »    Full Text »    PDF »
The DNA-bending protein, HMG1, is required for correct cleavage of 23 bp recombination signal sequences by recombination activating gene proteins in vitro.
T. Yoshida, A. Tsuboi, K.-i. Ishiguro, F. Nagawa, and H. Sakano (2000)
Int. Immunol. 12, 721-729
   Abstract »    Full Text »    PDF »
The Mechanism of Chromosome 7 Inversion in Human Lymphocytes Expressing Chimeric {gamma}{beta} TCR.
C. Retiere, F. Halary, M.-A. Peyrat, F. Le Deist, M. Bonneville, and M.-M. Hallet (1999)
J. Immunol. 162, 903-910
   Abstract »    Full Text »    PDF »
Decreased Frequency of Rearrangement due to the Synergistic Effect of Nucleotide Changes in the Heptamer and Nonamer of the Recombination Signal Sequence of the V{kappa} Gene A2b, Which Is Associated with Increased Susceptibility of Navajos to Haemophilus influenzae Type b Disease.
B. Nadel, A. Tang, G. Lugo, V. Love, G. Escuro, and A. J. Feeney (1998)
J. Immunol. 161, 6068-6073
   Abstract »    Full Text »    PDF »
Differential Usage of VH Gene Segments Is Mediated by cis Elements.
C. C. K. Yu, M. Larijani, I. N. Miljanic, and G. E. Wu (1998)
J. Immunol. 161, 3444-3454
   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 »
Sequence of the Spacer in the Recombination Signal Sequence Affects V(D)J Rearrangement Frequency and Correlates with Nonrandom V{kappa} Usage In Vivo.
B. Nadel, A. Tang, G. Escuro, G. Lugo, and A. J. Feeney (1998)
J. Exp. Med. 187, 1495-1503
   Abstract »    Full Text »    PDF »
Footprint Analysis of the RAG Protein Recombination Signal Sequence Complex for V(D)J Type Recombination.
F. Nagawa, K.-i. Ishiguro, A. Tsuboi, T. Yoshida, A. Ishikawa, T. Takemori, A. J. Otsuka, and H. Sakano (1998)
Mol. Cell. Biol. 18, 655-663
   Abstract »    Full Text »
Coding end sequence can markedly affect the initiation of V(D)J recombination..
R M Gerstein and M R Lieber (1993)
Genes & Dev. 7, 1459-1469
   Abstract »    PDF »
On somatic recombination in the central nervous system of transgenic mice.
A Abeliovich, D Gerber, O Tanaka, M Katsuki, A. Graybiel, and S Tonegawa (1992)
Science 257, 404-410
   PDF »
Detection of somatic DNA recombination in the transgenic mouse brain.
M Matsuoka, F Nagawa, K Okazaki, L Kingsbury, K Yoshida, U Muller, D. Larue, J. Winer, and H Sakano (1991)
Science 254, 81-86
   Abstract »    PDF »
NBP, a protein that specifically binds an enhancer of immunoglobulin gene rearrangement: purification and characterization..
M Li, E Morzycka-Wroblewska, and S V Desiderio (1989)
Genes & Dev. 3, 1801-1813
   Abstract »    PDF »
V(D)J recombination: a functional definition of the joining signals..
J E Hesse, M R Lieber, K Mizuuchi, and M Gellert (1989)
Genes & Dev. 3, 1053-1061
   Abstract »    PDF »
The scid gene encodes a trans-acting factor that mediates the rejoining event of Ig gene rearrangement..
E A Hendrickson, D G Schatz, and D T Weaver (1988)
Genes & Dev. 2, 817-829
   Abstract »    PDF »
Retroviruses.
H Varmus (1988)
Science 240, 1427-1435
   Abstract »    PDF »
Analysis of the V(D)J Recombination Efficiency at Lymphoid Chromosomal Translocation Breakpoints.
S. C. Raghavan, I. R. Kirsch, and M. R. Lieber (2001)
J. Biol. Chem. 276, 29126-29133
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)