|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 203-209
N-terminal truncated human RAG1 proteins can direct
T-cell receptor but not immunoglobulin gene rearrangements
Jeroen G. Noordzij,
Nicole S. Verkaik,
Nico G. Hartwig,
Ronald de Groot,
Dik C. van Gent, and
Jacques J. M. van Dongen
From the Department of Immunology, Erasmus University Rotterdam,
University Hospital Rotterdam-Dijkzigt; the Department of Cell Biology
and Genetics, Erasmus University Rotterdam; and the Department of
Pediatrics, Division of Infectious Diseases and Immunology, Sophia
Children's Hospital/University Hospital Rotterdam, Rotterdam, The
Netherlands.
The proteins encoded by RAG1 and RAG2 can
initiate gene recombination by site-specific cleavage of DNA in
immunoglobulin and T-cell receptor (TCR) loci. We identified a new
homozygous RAG1 gene mutation (631delT) that leads to a
premature stop codon in the 5' part of the RAG1 gene. The
patient carrying this 631delT RAG1 gene mutation died at the
age of 5 weeks from an Omenn syndrome-like T+/B
severe combined immunodeficiency disease. The high number of
blood T-lymphocytes (55 × 106/mL) showed an almost
polyclonal TCR gene rearrangement repertoire not of maternal origin. In
contrast, B-lymphocytes and immunoglobulin gene rearrangements were
hardly detectable. We showed that the 631delT RAG1 gene can
give rise to an N-terminal truncated RAG1 protein, using an internal
AUG codon as the translation start site. Consistent with the V(D)J
recombination in T cells, this N-terminal truncated RAG1 protein was
active in a plasmid V(D)J recombination assay. Apparently, the
N-terminal truncated RAG1 protein can recombine TCR genes but not
immunoglobulin genes. We conclude that the N-terminus of the RAG1
protein is specifically involved in immunoglobulin gene rearrangements.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Simkus, P. Anand, A. Bhattacharyya, and J. M. Jones
Biochemical and Folding Defects in a RAG1 Variant Associated with Omenn Syndrome
J. Immunol.,
December 15, 2007;
179(12):
8332 - 8340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Callebaut, L. Malivert, A. Fischer, J.-P. Mornon, P. Revy, and J.-P. de Villartay
Cernunnos Interacts with the XRCC4{middle dot}DNA-ligase IV Complex and Is Homologous to the Yeast Nonhomologous End-joining Factor Nej1
J. Biol. Chem.,
May 19, 2006;
281(20):
13857 - 13860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Swanson, D. Volkmer, and L. Wang
Full-length RAG-2, and Not Full-length RAG-1, Specifically Suppresses RAG-mediated Transposition but Not Hybrid Joint Formation or Disintegration
J. Biol. Chem.,
February 6, 2004;
279(6):
4034 - 4044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Jones and M. Gellert
Autoubiquitylation of the V(D)J recombinase protein RAG1
PNAS,
December 23, 2003;
100(26):
15446 - 15451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. D. Dudley, J. Sekiguchi, C. Zhu, M. J. Sadofsky, S. Whitlow, J. DeVido, R. J. Monroe, C. H. Bassing, and F. W. Alt
Impaired V(D)J Recombination and Lymphocyte Development in Core RAG1-expressing Mice
J. Exp. Med.,
November 3, 2003;
198(9):
1439 - 1450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Noordzij, N. S. Verkaik, M. van der Burg, L. R. van Veelen, S. de Bruin-Versteeg, W. Wiegant, J. M. J. J. Vossen, C. M. R. Weemaes, R. de Groot, M. Z. Zdzienicka, et al.
Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow
Blood,
February 15, 2003;
101(4):
1446 - 1452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Noordzij, S. de Bruin-Versteeg, N. S. Verkaik, J. M. J. J. Vossen, R. de Groot, E. Bernatowska, A. W. Langerak, D. C. van Gent, and J. J. M. van Dongen
The immunophenotypic and immunogenotypic B-cell differentiation arrest in bone marrow of RAG-deficient SCID patients corresponds to residual recombination activities of mutated RAG proteins
Blood,
August 28, 2002;
100(6):
2145 - 2152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Martin, D. Wolf-Eichbaum, G. Duinkerken, W. A. Scherbaum, H. Kolb, J. G. Noordzij, and B. O. Roep
Development of Type 1 Diabetes despite Severe Hereditary B-Cell Deficiency
N. Engl. J. Med.,
October 4, 2001;
345(14):
1036 - 1040.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Langerak, R. van den Beemd, I. L. M. Wolvers-Tettero, P. P. C. Boor, E. G. van Lochem, H. Hooijkaas, and J. J. M. van Dongen
Molecular and flow cytometric analysis of the V{beta} repertoire for clonality assessment in mature TCR{alpha}{beta} T-cell proliferations
Blood,
July 1, 2001;
98(1):
165 - 173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Corneo, D. Moshous, T. Gungor, N. Wulffraat, P. Philippet, F. L. Deist, A. Fischer, and J.-P. de Villartay
Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome
Blood,
May 1, 2001;
97(9):
2772 - 2776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Sadofsky
The RAG proteins in V(D)J recombination: more than just a nuclease
Nucleic Acids Res.,
April 1, 2001;
29(7):
1399 - 1409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
