Robust immunoglobulin class switch recombination and end joining in Parp9-deficient mice
| Autor: | Heng-Kuan Wong, Françoise Dantzer, Valérie Schreiber, Aurélia Noll, Bernardo Reina-San-Martin, José Yélamos, Léa Gaudot, Isabelle Robert |
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| Přispěvatelé: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antibody diversification DNA End-Joining Repair MESH: Immunoglobulins MESH: DNA Breaks Double-Stranded Poly (ADP-Ribose) Polymerase-1 MESH: Poly (ADP-Ribose) Polymerase-1 Adaptive Immunity MESH: Mice Knockout Mice chemistry.chemical_compound 0302 clinical medicine PARP1 Immunology and Allergy DNA Breaks Double-Stranded MESH: Animals Cells Cultured Polymerase Mice Knockout MESH: DNA Repair B-Lymphocytes Parp9 biology Cytidine deaminase 3. Good health Class switch recombination MESH: Immunoglobulin Class Switching Poly(ADP-ribose) Polymerases ADP-ribosylation MESH: Cells Cultured DNA damage DNA repair Immunology Immunoglobulins Immunoglobulin Class Switch Recombination 03 medical and health sciences MESH: Mice Inbred C57BL MESH: B-Lymphocytes Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice MESH: DNA Damage MESH: Poly(ADP-ribose) Polymerases MESH: DNA End-Joining Repair Immunoglobulin Class Switching Molecular biology Mice Inbred C57BL 030104 developmental biology chemistry Immunoglobulin class switching biology.protein DNA MESH: Adaptive Immunity DNA Damage 030215 immunology |
| Zdroj: | Eur J Immunol Eur J Immunol, 2017, 47 (4), pp.665-676. ⟨10.1002/eji.201646757⟩ |
| DOI: | 10.1002/eji.201646757⟩ |
| Popis: | To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving poly(ADP-ribose) polymerases Parp1, Parp2, and Parp3 to promote appropriate DNA repair and efficient long-range recombination. The macroParp Parp9, which is overexpressed in certain lymphomas, has been recently implicated in DSB repair, acting together with Parp1. Here, we examine the contribution of Parp9 to the resolution of physiological DSBs incurred during V(D)J recombination and CSR by generating Parp9-/- mice. We find that Parp9-deficient mice are viable, fertile, and do not show any overt phenotype. Moreover, we find that Parp9 is dispensable for B-cell development. Finally, we show that CSR and DNA end-joining are robust in the absence of Parp9, indicating that Parp9 is not essential in vivo to achieve physiological DSB repair, or that strong compensatory mechanisms exist. |
| Databáze: | OpenAIRE |
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