DNA fragmentation factor 45-deficient cells are more resistant to apoptosis and exhibit different dying morphology than wild-type control cells

The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric DNa se complex critical for the induction of DNA fragmentation in vitro, To und erstand the in vivo role of DFF45 in programmed cell death, we measured the expression of DFF45 during mouse development and compared DNA fragmentatio n and viability of DFF45-deficient cells with wild-type control cells after activation of apoptosis, We found that DFF45 is ubiquitously expressed thr oughout mouse development, Moreover, DFF45-deficient thymocytes are resista nt to DNA fragmentation with in vivo dexamethasone treatment, Furthermore, primary thymocytes from DFF45 mutant mice are also more resistant to apopto sis than wild-type control cells on exposure to several apoptotic stimuli. Dying DFF45-deficient thymocytes exhibit different morphology than wild-typ e control cells in that they show reduced degree of chromatin condensation, absent nuclear fragmentation, intranuclear cytoplasmic invagination, and s triking nuclear chromatin conglutination after release from disintegrating cells. These results indicate that DFF45 is essential during normal apoptos is.