Ultraviolet light-induced G2 phase cell cycle checkpoint blocks cdc25-dependent progression into mitosis.
In response to low doses of ultraviolet (U.V.) radiation, cells undergo a G2 delay. In this study we have shown that the G2 delay results in the accumulation of inactive forms of cyclin B1/cdc2 and both the G2 and mitotic complexes of cyclin A/cdk. This appears to be through a block in the cdc25-dependent activation of these complexes. The expression and localisation of cyclin A and cyclin B1/cdk complexes are similar in U.V.-induced G2 delay and normal early G2 phase cells. Cdc25B and cdc25C also accumulate to normal G2 levels in U.V. irradiated cells, but the mitotic phosphorylation associated with increased activity of both cdc25B and cdc25C is absent. The cdc25B accumulates in the nucleus of U.V. irradiated cells and in normal G2 phase cells. Thus the block in cyclin B/cdc2 activation is in part due to the physical separation of cyclin B/cdc2, localised in the cytoplasm, from the cdc25B and cdc25C phosphatases localised in the nucleus. The data positions the U.V.-induced G2 checkpoint at either the S/G2 transition or early G2 phase, prior to the activation of cyclin A/cdk2.
Gabrielli
B G
BG
Queensland Cancer Fund Research Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Australia.
Clark
J M
JM
McCormack
A K
AK
Ellem
K A
KA
D016203:CDC2 Protein Kinase / Q000378:metabolism / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism / Q000528:radiation effects*; D016195:G2 Phase / Q000528:radiation effects*; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D016196:S Phase / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases
C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases