Requirement for p53 and p21 to sustain G2 arrest after DNA damage.
After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma radiated cells progressed into mitosis and exhibited a G2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells.
Bunz
F
F
The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
Dutriaux
A
A
Lengauer
C
C
Waldman
T
T
Zhou
S
S
Brown
J P
JP
Sedivy
J M
JM
Kinzler
K W
KW
Vogelstein
B
B
D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D016195:G2 Phase / Q000187:drug effects; D005720:Gamma Rays; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D008938:Mitosis; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D004247:DNA; D016203:CDC2 Protein Kinase; D015739:Nocodazole