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

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.
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The Journal of Experimental Medecine, The Rockefeller University Press, 2009, 206 (5), pp.1047-56. 〈10.1084/jem.20082468〉
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Soumis le : lundi 25 mai 2009 - 15:25:42
Dernière modification le : jeudi 11 janvier 2018 - 06:22:44

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Isabelle Robert, Françoise Dantzer, Bernardo Reina-San-Martin. Parp1 facilitates alternative NHEJ, whereas Parp2 suppresses IgH/c-myc translocations during immunoglobulin class switch recombination.. The Journal of Experimental Medecine, The Rockefeller University Press, 2009, 206 (5), pp.1047-56. 〈10.1084/jem.20082468〉. 〈inserm-00387515〉

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