A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p
V(D)J recombination, accountable for the diversity of T cell receptor- and immunoglobulin-encoding genes, is initiated by a lymphoid-specific DNA double-strand break. The general DNA repair machinery is responsible for the resolution of this break. Any defect in one of the known components of the DN...
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fthighwire:oai:open-archive.highwire.org:hmg:9/4/583 2023-05-15T15:26:10+02:00 A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p Moshous, Despina Li, Lanying Chasseval, Régina de Philippe, Noel Jabado, Nada Cowan, Morton J. Fischer, Alain Villartay, Jean-Pierre de 2000-03-01 00:00:00.0 text/html http://hmg.oxfordjournals.org/cgi/content/short/9/4/583 https://doi.org/10.1093/hmg/9.4.583 en eng Oxford University Press http://hmg.oxfordjournals.org/cgi/content/short/9/4/583 http://dx.doi.org/10.1093/hmg/9.4.583 Copyright (C) 2000, Oxford University Press ARTICLES TEXT 2000 fthighwire https://doi.org/10.1093/hmg/9.4.583 2016-11-16T17:02:38Z V(D)J recombination, accountable for the diversity of T cell receptor- and immunoglobulin-encoding genes, is initiated by a lymphoid-specific DNA double-strand break. The general DNA repair machinery is responsible for the resolution of this break. Any defect in one of the known components of the DNA repair/V(D)J recombination machinery (Ku70, Ku80, DNA-PKcs, XRCC4 and DNA ligase IV) leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and ultimately to severe combined immune deficiency (SCID) in several animal models. A human SCID condition is also characterized by an absence of mature T and B lymphocytes, and is associated with an increase in sensitivity to DNA-damaging agents (RS-SCID). None of the above-mentioned genes are defective in these patients, arguing for the likelihood of the existence of yet another unknown component of the V(D)J recombination/DNA repair apparatus. Athabascan-speaking (SCIDA) Navajo and Apache Native Americans have a very high incidence of T–B– SCID. The SCIDA locus is highly linked with markers on chromosome 10p, although the exact molecular defect has not been recognized in these patients. We show here that cells with the SCIDA defect are impaired in the DNA repair phase of V(D)J recombination similarly to RS-SCID, precisely an absence of V(D)J coding joint formation. Moreover, genotyping analysis in several RS-SCID families corroborates a linkage of the RS-SCID locus to the SCIDA region on chromosome 10p. These results demonstrate the presence of a new essential DNA repair/V(D)J recombination gene in this region, the mutation of which causes RS-SCID in humans. Text Athabascan HighWire Press (Stanford University) Human Molecular Genetics 9 4 583 588 |
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ARTICLES Moshous, Despina Li, Lanying Chasseval, Régina de Philippe, Noel Jabado, Nada Cowan, Morton J. Fischer, Alain Villartay, Jean-Pierre de A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
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ARTICLES |
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V(D)J recombination, accountable for the diversity of T cell receptor- and immunoglobulin-encoding genes, is initiated by a lymphoid-specific DNA double-strand break. The general DNA repair machinery is responsible for the resolution of this break. Any defect in one of the known components of the DNA repair/V(D)J recombination machinery (Ku70, Ku80, DNA-PKcs, XRCC4 and DNA ligase IV) leads to abortion of the V(D)J rearrangement process, early block in both T and B cell maturation, and ultimately to severe combined immune deficiency (SCID) in several animal models. A human SCID condition is also characterized by an absence of mature T and B lymphocytes, and is associated with an increase in sensitivity to DNA-damaging agents (RS-SCID). None of the above-mentioned genes are defective in these patients, arguing for the likelihood of the existence of yet another unknown component of the V(D)J recombination/DNA repair apparatus. Athabascan-speaking (SCIDA) Navajo and Apache Native Americans have a very high incidence of T–B– SCID. The SCIDA locus is highly linked with markers on chromosome 10p, although the exact molecular defect has not been recognized in these patients. We show here that cells with the SCIDA defect are impaired in the DNA repair phase of V(D)J recombination similarly to RS-SCID, precisely an absence of V(D)J coding joint formation. Moreover, genotyping analysis in several RS-SCID families corroborates a linkage of the RS-SCID locus to the SCIDA region on chromosome 10p. These results demonstrate the presence of a new essential DNA repair/V(D)J recombination gene in this region, the mutation of which causes RS-SCID in humans. |
format |
Text |
author |
Moshous, Despina Li, Lanying Chasseval, Régina de Philippe, Noel Jabado, Nada Cowan, Morton J. Fischer, Alain Villartay, Jean-Pierre de |
author_facet |
Moshous, Despina Li, Lanying Chasseval, Régina de Philippe, Noel Jabado, Nada Cowan, Morton J. Fischer, Alain Villartay, Jean-Pierre de |
author_sort |
Moshous, Despina |
title |
A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
title_short |
A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
title_full |
A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
title_fullStr |
A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
title_full_unstemmed |
A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p |
title_sort |
new gene involved in dna double-strand break repair and v(d)j recombination is located on human chromosome 10p |
publisher |
Oxford University Press |
publishDate |
2000 |
url |
http://hmg.oxfordjournals.org/cgi/content/short/9/4/583 https://doi.org/10.1093/hmg/9.4.583 |
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Athabascan |
genre_facet |
Athabascan |
op_relation |
http://hmg.oxfordjournals.org/cgi/content/short/9/4/583 http://dx.doi.org/10.1093/hmg/9.4.583 |
op_rights |
Copyright (C) 2000, Oxford University Press |
op_doi |
https://doi.org/10.1093/hmg/9.4.583 |
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Human Molecular Genetics |
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9 |
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1766356715051155456 |