NUCLEAR EXPORT OF CYCLIN B1 AND ITS POSSIBLE ROLE IN THE DNA DAMAGE-INDUCED G(2) CHECKPOINT

M-phase-promoting factor (MPF), a complex of cdc2 and a B-type cyclin, is a key regulator of the G(2)/M cell cycle transition. Cyclin B1 acc umulates in the cytoplasm through S and G(2) phases and translocates t o the nucleus during prophase, We show here that cytoplasmic localizat ion of cyclin B1 during interphase is directed by its nuclear export s ignal (NES)-dependent transport mechanism. Treatment of HeLa cells wit h leptomycin B (LMB), a specific inhibitor of the NES-dependent transp ort, resulted in nuclear accumulation of cyclin B1 in G(2) phase. Disr uption of an NES which has been identified in cyclin B1 here abolished the nuclear export of this protein, and consequently the NES-disrupte d cyclin B1 when expressed in cells accumulated in the nucleus. Moreov er, we show that expression of the NES-disrupted cyclin B1 or LMB trea tment of the cells is able to override the DNA damage-induced G(2) che ckpoint when combined with caffeine treatment. These results suggest a role of nuclear exclusion of cyclin B1 in the DNA damage-induced G(2) checkpoint.