Fiche publication
Date publication
mai 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DANTZER Françoise
,
Dr REINA-SAN-MARTIN Bernardo
Tous les auteurs :
Robert I, Dantzer F, Reina-San-Martin B
Lien Pubmed
Résumé
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.
Référence
J Exp Med. 2009 May 11;206(5):1047-56
