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  • The EMBO Journal (2006) 25, 4350 - 4360
  • doi:10.1038/sj.emboj.7601301

Published online: 31 August 2006

PARP-2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes

José Yélamos1,6, Yolanda Monreal2,6, Luis Saenz2, Enrique Aguado1, Valérie Schreiber3, Rubén Mota2, Teodomiro Fuente2, Alfredo Minguela4, Pascual Parrilla2, Gilbert de Murcia3, Elena Almarza5, Pedro Aparicio1 and Josiane Ménissier-de Murcia3

  1. Department of Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Murcia, Murcia, Spain
  2. Transplant Unit, University Hospital 'Virgen de la Arrixaca', Murcia, Spain
  3. UPR 9003 du Centre National de la Recherche Scientifique, Strasbourg, France
  4. Immunology Unit, University Hospital 'Virgen de la Arrixaca', Murcia, Spain
  5. CIEMAT, Madrid, Spain
  6. These authors contributed equally to this work

Correspondence to:

José Yélamos, Departamento de Bioquímica, Biología Molecular e Inmunología, Facultad de Medicina, Campus de Espinardo, Apartado de Correos 4021, Universidad de Murcia, 30100-Murcia, Spain. Tel.: +34 968 369090; Fax: +34 968 369678; E-mail: jyelamos@um.es

Josiane Ménissier-de Murcia, UPR 9003 du Centre National de la Recherche Scientifique, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP10413, 67412 Illkirch, Strasbourg, France. Tel.: +33 390 244704; Fax: +33 390 244686; E-mail: josiane@esbs.u-strasbg.fr

Received 10 April 2006; Accepted 1 August 2006

Poly-(ADP-ribose) polymerase-2 (PARP-2) belongs to a large family of enzymes that synthesize and transfer ADP-ribose polymers to acceptor proteins, modifying their functional properties. PARP-2-deficient (Parp-2-/-) cells, similar to Parp-1-/- cells, are sensitive to both ionizing radiation and alkylating agents. Here we show that inactivation of mouse Parp-2, but not Parp-1, produced a two-fold reduction in CD4+CD8+ double-positive (DP) thymocytes associated with decreased DP cell survival. Microarray analyses revealed increased expression of the proapoptotic Bcl-2 family member Noxa in Parp-2-/- DP thymocytes compared to littermate controls. In addition, DP thymocytes from Parp-2-/- have a reduced expression of T-cell receptor (TCR)alpha and a skewed repertoire of TCRalpha toward the 5' Jalpha segments. Our results show that in the absence of PARP-2, the survival of DP thymocytes undergoing TCRalpha recombination is compromised despite normal amounts of Bcl-xL. These data suggest a novel role for PARP-2 as an important mediator of T-cell survival during thymopoiesis by preventing the activation of DNA damage-dependent apoptotic response during the multiple rounds of TCRalpha rearrangements preceding a positively selected TCR.

  • Keywords:

    • apoptosis,
    • BH3-only proteins,
    • Noxa,
    • PARP-2,
    • TCRalpha rearrangement