|
|
Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-01-0187.
Submitted January 25, 2002
Accepted September 22, 2002
Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-BCR checkpoint in bone marrow
Jeroen G Noordzij, Nicole S Verkaik, Mirjam van der Burg, Lieneke R van Veelen, Sandra de Bruin-Versteeg, Wouter Wiegant, Jaak M J J Vossen, Corry M R Weemaes, Ronald de Groot, Malgorzata Z Zdzienicka, Dik C van Gent, and Jacques J M van Dongen*
Department of Immunology, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Cell Biology and Genetics, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Pediatric Immunology and Infectious Diseases, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Leiden, The Netherlands
Department of Radiation Oncology, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands
Ludwik Rydygier University of Medical Sciences, Bydgoszcz, Poland
* Corresponding author; email: vandongen{at}immu.fgg.eur.nl.
Severe combined immunodeficiency disease (SCID) can be immunologically classified by the absence or presence of T, B, and NK-cells. About 30% of T-B-NK+ SCID patients carry mutations in the recombination activating genes (RAG). Some T-B-NK+ SCID patients without RAG gene mutations are sensitive to ionizing radiation and several of these radiosensitive (RS)-SCID patients were recently shown to have large deletions or truncation mutations in the Artemis gene, implying a role for Artemis in DNA double strand break (dsb) repair.
We identified five RS-SCID patients without RAG gene mutations, four of them with Artemis gene mutations. One patient had a large genomic deletion, but the other three patients carried simple missense mutations in conserved amino acid residues in the SNM1 homology domain of the Artemis protein. Extrachromosomal V(D)J recombination assays showed normal and precise signal joint formation, but inefficient coding joint formation in fibroblasts of these patients, which could be complemented by the wild-type Artemis gene. The cells containing the missense mutations in the SNM1 homology domain had the same recombination phenotype as the cells with the large deletion, indicating that these amino acid residues are indispensable for Artemis function. Immunogenotyping and immunophenotyping of bone marrow samples of two RS-SCID patients showed the absence of complete VH-JH gene rearrangements and consequently a complete B-cell differentiation arrest at the pre-BCR checkpoint, i.e. at the transition from CyIgµ- pre-B-I-cells to CyIgµ+ pre-B-II-cells. The completeness of this arrest illustrates the importance of Artemis at this stage of lymphoid differentiation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Du, M. van der Burg, S. W. Popov, A. Kotnis, J. J.M. van Dongen, A. R. Gennery, and Q. Pan-Hammarstrom
Involvement of Artemis in nonhomologous end-joining during immunoglobulin class switch recombination
J. Exp. Med.,
December 22, 2008;
205(13):
3031 - 3040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hejna, S. Philip, J. Ott, C. Faulkner, and R. Moses
The hSNM1 protein is a DNA 5'-exonuclease
Nucleic Acids Res.,
September 25, 2007;
35(18):
6115 - 6123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. J. McAlister and R. A. Owens
Preferential Integration of Adeno-Associated Virus Type 2 into a Polypyrimidine/Polypurine-Rich Region within AAVS1
J. Virol.,
September 15, 2007;
81(18):
9718 - 9726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Niewolik, U. Pannicke, H. Lu, Y. Ma, L.-C. V. Wang, P. Kulesza, E. Zandi, M. R. Lieber, and K. Schwarz
DNA-PKcs Dependence of Artemis Endonucleolytic Activity, Differences between Hairpins and 5' or 3' Overhangs
J. Biol. Chem.,
November 10, 2006;
281(45):
33900 - 33909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Liu, C. A. J. Vosshenrich, C. Lagresle-Peyrou, M. Malassis-Seris, C. Hue, A. Fischer, J. P. Di Santo, and M. Cavazzana-Calvo
Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients
Blood,
August 15, 2006;
108(4):
1123 - 1128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ege, Y. Ma, B. Manfras, K. Kalwak, H. Lu, M. R. Lieber, K. Schwarz, and U. Pannicke
Omenn syndrome due to ARTEMIS mutations
Blood,
June 1, 2005;
105(11):
4179 - 4186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rooney, J. Sekiguchi, S. Whitlow, M. Eckersdorff, J. P. Manis, C. Lee, D. O. Ferguson, and F. W. Alt
Artemis and p53 cooperate to suppress oncogenic N-myc amplification in progenitor B cells
PNAS,
February 24, 2004;
101(8):
2410 - 2415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. N. Mahajan and B. S. Mitchell
Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase
PNAS,
September 16, 2003;
100(19):
10746 - 10751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mansilla-Soto and P. Cortes
VDJ Recombination: Artemis and Its In Vivo Role in Hairpin Opening
J. Exp. Med.,
March 3, 2003;
197(5):
543 - 547.
[Full Text]
[PDF]
|
|
|
|
|
