Parp1 facilitates alternative NHEJ, whereas Parp2 suppresses IgH/c-myc translocations during immunoglobulin class switch recombination

Author:

Robert Isabelle1,Dantzer Françoise2,Reina-San-Martin Bernardo1

Affiliation:

1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of Cancer Biology. Institut National de la Santé et de la Recherche Médicale U964-Centre National de la Recherche Scientifique UMR7104, Université de Strasbourg, 67404 Illkirch, France

2. Poly(ADP-ribosyl)ation et Intégrité du Génome, IREBS-FRE3211 Centre National de la Recherche Scientifique, Université de Strasbourg, Ecole Supérieure de Biotechnologie de Strasbourg, 67412 Illkirch, France

Abstract

Immunoglobulin class switch recombination (CSR) is initiated by DNA breaks triggered by activation-induced cytidine deaminase (AID). These breaks activate DNA damage response proteins to promote appropriate repair and long-range recombination. Aberrant processing of these breaks, however, results in decreased CSR and/or increased frequency of illegitimate recombination between the immunoglobulin heavy chain locus and oncogenes like c-myc. Here, we have examined the contribution of the DNA damage sensors Parp1 and Parp2 in the resolution of AID-induced DNA breaks during CSR. We find that although Parp enzymatic activity is induced in an AID-dependent manner during CSR, neither Parp1 nor Parp2 are required for CSR. We find however, that Parp1 favors repair of switch regions through a microhomology-mediated pathway and that Parp2 actively suppresses IgH/c-myc translocations. Thus, we define Parp1 as facilitating alternative end-joining and Parp2 as a novel translocation suppressor during CSR.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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