ArticleMolecular and cellular biology2010
Dual functions of Nbs1 in the repair of DNA breaks and proliferation ensure proper V(D)J recombination and T-cell development.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Immune dysfunction in nucleotide excision repair disorders: an underrecognized clinical phenotype with relevance for inborn errors of immunity.Frontiers in immunology · 2026Review
- Differential expression of a disease-associated MRE11 variant reveals distinct phenotypic outcomes.Human molecular genetics · 2025Article
- Differential expression of a disease-associatedbioRxiv : the preprint server for biology · 2025Article
- Nbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.Cell proliferation · 2021Article
- T Lymphocytes in Patients With Nijmegen Breakage Syndrome Demonstrate Features of Exhaustion and Senescence in Flow Cytometric Evaluation of Maturation Pathway.Frontiers in immunology · 2020Article
- Telomeric epigenetic response mediated by Gadd45a regulates stem cell aging and lifespan.EMBO reports · 2018Article
- DNA Damage Response in Hematopoietic Stem Cell Ageing.Genomics, proteomics & bioinformatics · 2016Review
- Defining ATM-Independent Functions of the Mre11 Complex with a Novel Mouse Model.Molecular cancer research : MCR · 2016Article
- Inactivation of nuclear GSK3β by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response.Nature communications · 2016Article
- Programmed DNA breaks in lymphoid cells: repair mechanisms and consequences in human disease.Immunology · 2016Review
- DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation.PLoS genetics · 2015Article
- Article
- The response to and repair of RAG-mediated DNA double-strand breaks.Annual review of immunology · 2012Review
- ATMIN is required for maintenance of genomic stability and suppression of B cell lymphoma.Cancer cell · 2011Article
- The MRE11 complex: starting from the ends.Nature reviews. Molecular cell biology · 2011Review
- PID comes full circle: applications of V(D)J recombination excision circles in research, diagnostics and newborn screening of primary immunodeficiency disorders.Frontiers in immunology · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Immunodeficiency and lymphoid malignancy are hallmarks of the human disease Nijmegen breakage syndrome (NBS; OMIM 251260), which is caused by NBS1 mutations. Although NBS1 has been shown to bind to the T-cell receptor alpha (TCRα) locus, its role in TCRβ rearrangement is unclear. Hypomorphic mutations of Nbs1 in mice and patients result in relatively mild T-cell deficiencies, raising the question of whether the truncated Nbs1 protein might have clouded a certain function of NBS1 in T-cell development. Here we show that the deletion of the entire Nbs1 protein in T-cell precursors (Nbs1(T-del)) results in severe lymphopenia and a hindrance to the double-negative 3 (DN3)-to-DN4 transition in early T-cell development, due to abnormal TCRβ coding and signal joints as well as the functions of Nbs1 in T-cell expansion. Chromatin immunoprecipitation (ChIP) analysis of the TCR loci reveals that Nbs1 depletion compromises the loading of Mre11/Rad50 to V(D)J-generated DNA double-strand breaks (DSBs) and thereby affects resection of DNA termini and chromatin conformation of the postcleavage complex. Although a p53 deficiency relieves the DN3→DN4 transition block, neither a p53 deficiency nor ectopic expression of TCRαβ rescues the major T-cell loss in Nbs1(T-del) mice. All together, these results demonstrate that Nbs1's functions in both repair of V(D)J-generated DSBs and proliferation are essential for T-cell development.
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