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Nuclear export of cyclin B1 and its possible role in the DNA damage‐induced G 2 checkpoint
Author(s) -
Toyoshima Fumiko,
Moriguchi Tetsuo,
Wada Atsushi,
Fukuda Makoto,
Nishida Eisuke
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.10.2728
Subject(s) - biology , g2 m dna damage checkpoint , dna damage , chek1 , nuclear export signal , microbiology and biotechnology , dna , cell cycle checkpoint , cyclin , nuclear protein , genetics , cancer research , computational biology , cell cycle , cell nucleus , transcription factor , gene
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 accumulates in the cytoplasm through S and G 2 phases and translocates to the nucleus during prophase. We show here that cytoplasmic localization of cyclin B1 during interphase is directed by its nuclear export signal (NES)‐dependent transport mechanism. Treatment of HeLa cells with leptomycin B (LMB), a specific inhibitor of the NES‐dependent transport, resulted in nuclear accumulation of cyclin B1 in G 2 phase. Disruption of an NES which has been identified in cyclin B1 here abolished the nuclear export of this protein, and consequently the NES‐disrupted cyclin B1 when expressed in cells accumulated in the nucleus. Moreover, we show that expression of the NES‐disrupted cyclin B1 or LMB treatment of the cells is able to override the DNA damage‐induced G 2 checkpoint when combined with caffeine treatment. These results suggest a role of nuclear exclusion of cyclin B1 in the DNA damage‐induced G 2 checkpoint.