Delayed cyclin B1 expression during the G2 arrest following DNA damage.

Exposure of cells to DNA damaging agents results in a G2 arrest. Exposure of HeLa cells to camptothecin, etoposide or nitrogen mustard for 1 h in S phase resulted in delayed expression of cyclin B1 mRNA during the G2 arrest. Initially the levels of cyclin B1 protein were low as well; however, with extended time the cells blocked in G2 regained higher levels of cyclin B1 protein. In the case of cells treated with nitrogen mustard the higher levels coincided with cells exiting the G2 block into G1. However, with camptothecin or etoposide treatment, while the accumulation of cyclin B1 protein was delayed, its levels eventually surpassed peak levels seen in control cells, in spite of the fact that cells were still blocked in G2. These cells did not continue to progress through the cell cycle indicating further complexity to the mechanisms underlying the G2 block. Decreased transcription and stability of cyclin B1 mRNA were shown to occur after treatment with these DNA damaging agents. These results indicate that suppression of cyclin B1 mRNA expression is one consequence of DNA damage in HeLa cells.