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PARP‐2 deficiency affects the survival of CD4 + CD8 + double‐positive thymocytes
Author(s) -
Yélamos José,
Monreal Yolanda,
Saenz Luis,
Aguado Enrique,
Schreiber Valérie,
Mota Rubén,
Fuente Teodomiro,
Minguela Alfredo,
Parrilla Pascual,
de Murcia Gilbert,
Almarza Elena,
Aparicio Pedro,
Ménissierde Murcia Josiane
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601301
Subject(s) - biology , poly adp ribose polymerase , cd8 , t cell receptor , microbiology and biotechnology , thymocyte , apoptosis , double negative , dna damage , t cell , dna repair , cancer research , enzyme , immunology , polymerase , immune system , genetics , dna , biochemistry
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)α and a skewed repertoire of TCRα toward the 5′ Jα segments. Our results show that in the absence of PARP‐2, the survival of DP thymocytes undergoing TCRα recombination is compromised despite normal amounts of Bcl‐x L . 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 TCRα rearrangements preceding a positively selected TCR.