| First Author | Yélamos J | Year | 2006 |
| Journal | EMBO J | Volume | 25 |
| Issue | 18 | Pages | 4350-60 |
| PubMed ID | 16946705 | Mgi Jnum | J:113101 |
| Mgi Id | MGI:3664502 | Doi | 10.1038/sj.emboj.7601301 |
| Citation | Yelamos J, et al. (2006) PARP-2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes. EMBO J 25(18):4350-60 |
| abstractText | 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. |
