title: Robust immunoglobulin class switch recombination and end joining in Parp9-deficient mice.
abstract: 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.|Centre National de Recherche Scientifique, UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robert
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.|Centre National de Recherche Scientifique, UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Gaudot
authors.affiliation: Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.|Department of Immunology, Hospital del Mar, Barcelona, Spain.|Network Center for Biomedical Research on Hepatic and Digestive Diseases, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Yélamos
authors.affiliation: Centre National de Recherche Scientifique, UMR7242, Illkirch, France.|Laboratoire d'Excellence Medalis, Université de Strasbourg, Illkirch, France.|Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Illkirch, France.|Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Noll
authors.affiliation: Centre National de Recherche Scientifique, UMR7242, Illkirch, France.|Laboratoire d'Excellence Medalis, Université de Strasbourg, Illkirch, France.|Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Illkirch, France.|Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
authors.forename: Heng-Kuan
authors.initials: HK
authors.lastname: Wong
authors.affiliation: Centre National de Recherche Scientifique, UMR7242, Illkirch, France.|Laboratoire d'Excellence Medalis, Université de Strasbourg, Illkirch, France.|Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Illkirch, France.|Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
authors.affiliation: Centre National de Recherche Scientifique, UMR7242, Illkirch, France.|Laboratoire d'Excellence Medalis, Université de Strasbourg, Illkirch, France.|Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Illkirch, France.|Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.|Centre National de Recherche Scientifique, UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Reina-San-Martin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004260:DNA Repair; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007136:Immunoglobulins; C529384:Parp9 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: ADP-ribosylation; Antibody diversification; Class switch recombination; DNA repair; Parp9