Transient failure to dephosphorylate the cdc2-cyclin B1 complex accompanies radiation-induced G2-phase arrest in HeLa cells.
Ionizing radiation causes a division delay in mammalian cells, dominated by a period of G2-phase arrest. The G2- to M-phase transition in dividing mammalian cells is dependent on the kinase activity of the cdc2-cyclin B protein complex. In the present investigation we measured the quantities of these two proteins, the formation of their complex and the kinase activity of the complex as a function of cell age in the cell cycle for irradiated and control mammalian cell populations. The human HeLa S3 cells were synchronized at the G1/S-phase border by double thymidine block and exposed 3 h after release to 1.75 Gy of X rays. Studies of HeLa cells at other laboratories have shown that, for doses of 5 Gy or more, division delay is associated with a suppression of production of cyclin B mRNA. Here we report that, for cells irradiated with low doses, there is a transient failure of the complex to activate which correlates with the duration of radiation-induced G2-phase arrest. The irradiated cells showed an increase in both cyclin B and phosphorylated cdc2 over the levels in control cells, and both persisted for a much longer period than in controls, further confirmation of delay in the activation of the catalytic subunit.
Metting
N F
NF
Laboratory of Radiobiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Little
J B
JB
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D016195:G2 Phase / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation
D016213:Cyclins; D016203:CDC2 Protein Kinase