Cyclin B1 availability is a rate-limiting component of the radiation-induced G2 delay in HeLa cells.
Irradiation of tumor cells results in a G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is marked in HeLa and other cells by delayed expression of cyclin B1. To test whether this depression of cyclin B1 contributes to the G2 delay, we induced cyclin B1 expression in irradiated HeLa cells using a dexamethasone-inducible promoter. Induction of cyclin B1 after radiation abrogated the G2 delay by approximately doubling the rate at which the cells reentered mitosis, whereas dexamethasone itself had no effect. However, overexpression of cyclin B1 did not eliminate the G2 delay in irradiated cells. In unirradiated cells, overexpression of cyclin B1 had no effect on cell cycle progression. Confirmation that reduction of cyclin B1 levels would prolong G2 was provided using antisense oligonucleotides to cyclin B1. These results demonstrate that cyclin B1 levels control the length of the G2 delay following irradiation in HeLa cells but do not exclude additional mechanisms controlling the mitotic delay after irradiation.
Kao
G D
GD
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
McKenna
W G
WG
Maity
A
A
Blank
K
K
Muschel
R J
RJ
D015415:Biomarkers; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D005822:Genetic Vectors; D005938:Glucocorticoids / Q000494:pharmacology; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008938:Mitosis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D015415:Biomarkers; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D005938:Glucocorticoids; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D003907:Dexamethasone