Figure 9.

Model for increased apoptosis of DP thymocytes in Parp-2^−/− mice. In the absence of PARP-2, the repair of DSBs generated during Vα to Jα rearrangements could be affected. This could activate a physiological DNA damage-induced cellular apoptotic pathway leading to transcriptional upregulation of the proapoptotic BH3-only proteins Noxa and, to a lesser extent, Puma, which are critical initiators of cell death. Increased apoptosis would affect the lifespan of DP thymocytes and as a consequence impair secondary Vα to Jα rearrangements.