ROLE FOR E2F IS DNA DAMAGE-INDUCED ENTRY OF CELLS INTO S-PHASE

Mammalian cells respond to ionizing radiation (IR) with transient cell cycle arrest and induction of apoptosis. Here we show that IR increas es the expression of the E2F-1 transcription factor and the entry of c ells into S phase. E2F-1 transactivation function is inhibited bg cycl in A-kinase to ensure orderly progression through S phase. However, in contrast to proliferating cells, IR treatment results in down-regulat ion of cyclin A-kinase, Expression of a dominant negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of E2F in IR- induced S-phase entry. These findings also support opposing signals in volving the induction of E2F and the down-regulation of cyclin A-kinas e in the IR response.