A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination
| العنوان: | A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination |
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| المؤلفون: | Noel F C C de Miranda, Elin Enervald, Lennart Hammarström, Anne Durandy, Sven Kracker, Lena Ström, Josephine Wincent, Valérie Cormier-Daire, Torkild Visnes, Dik C. van Gent, Andrea Björkman, Jacqueline Schoumans, Juan Pié, Likun Du, Guntram Borck, Qiang Pan-Hammarström, Laurence Colleaux, Jean-Pierre de Villartay, Beatriz Puisac, Emma Lindgren |
| المساهمون: | European Molecular Biology Laboratory, Division of Immunology and The Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Department of Mathematical Sciences, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Universität Ulm - Ulm University [Ulm, Allemagne], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Molecular Genetics |
| المصدر: | Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2013, 210 (12), pp.2503-2513. ⟨10.1084/jem.20130168⟩ Journal of Experimental Medicine, 210(12), 2503-2513. Rockefeller University Press The Journal of Experimental Medicine The Journal of experimental medicine, vol. 210, no. 12, pp. 2503-2513 |
| بيانات النشر: | HAL CCSD, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Heterozygote, DNA End-Joining Repair, Adolescent, Chromosomal Proteins, Non-Histone, Molecular Sequence Data, Immunology, Cell Cycle Proteins, B-Lymphocytes/immunology, B-Lymphocytes/metabolism, Base Sequence, Case-Control Studies, Cell Cycle Proteins/metabolism, Cell Line, Child, Child, Preschool, Chromosomal Proteins, Non-Histone/metabolism, DNA/genetics, DNA/metabolism, DNA Breaks, Double-Stranded, De Lange Syndrome/genetics, De Lange Syndrome/immunology, De Lange Syndrome/metabolism, Humans, Immunoglobulin Class Switching, Infant, Intracellular Signaling Peptides and Proteins/metabolism, Mutation, Proteins/genetics, Proteins/metabolism, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae/metabolism, Tumor Suppressor p53-Binding Protein 1, Saccharomyces cerevisiae, Biology, Immunoglobulin Class Switch Recombination, 03 medical and health sciences, 0302 clinical medicine, De Lange Syndrome, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, Cohesin loading, B-Lymphocytes, 0303 health sciences, Cohesin, fungi, V(D)J recombination, Brief Definitive Report, Intracellular Signaling Peptides and Proteins, Proteins, NIPBL, DNA, 3. Good health, Establishment of sister chromatid cohesion, Non-homologous end joining, enzymes and coenzymes (carbohydrates), [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biological phenomena, cell phenomena, and immunity, Homologous recombination, 030215 immunology |
| الوصف: | The cohesin loading protein is required for nonhomologous end joining of double-strand DNA breaks DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-1007 1540-9538 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::73e11bf4b4a353b6e802ddd7cbdb8cd9Test https://hal.archives-ouvertes.fr/hal-02142266Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....73e11bf4b4a353b6e802ddd7cbdb8cd9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00221007 15409538 |
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