The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Characterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption
Open accessAbstract
The p53 tumor suppressor gene product is known to act as part of a cell cycle checkpoint in G1 following DNA damage. In order to investigate a proposed novel role for p53 as a checkpoint at mitosis following disruption of the mitotic spindle, we have used time-lapse videomicroscopy to show that both p53+/+ and p53-/- murine fibroblasts treated with the spindle drug nocodazole undergo transient arrest at mitosis for the same length of time. Thus, p53 does not participate in checkpoint function at mitosis. However, p53 does play a critical role in nocodazole-treated cells which have exited mitotic arrest without undergoing cytokinesis and have thereby adapted. We have determined that in nocodazole-treated, adapted cells, p53 is required during a specific time window to prevent cells from reentering the cell cycle and initiating another round of DNA synthesis. Despite having 4N DNA content, adapted cells are similar to G1 cells in that they have upregulated cyclin E expression and hypophosphorylated Rb protein. The mechanism of the p53-dependent arrest in nocodazole-treated adapted cells requires the cyclin-dependent kinase inhibitor p21, as p21-/- fibroblasts fail to arrest in response to nocodazole treatment and become polyploid. Moreover, p21 is required to a similar extent to maintain cell cycle arrest after either nocodazole treatment or irradiation. Thus, the p53-dependent checkpoint following spindle disruption functionally overlaps with the p53-dependent checkpoint following DNA damage.
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Cites
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“After irradiation, cells undergo p53-dependent arrest in G1 (20, 21, 23); after nocodazole-induced disruption of the mitotic spindle, cells arrest transiently at mitosis, adapt into a G1-like state, and then undergo p53-dependent arrest (33).”
BackgroundSelf-citationMice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
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Radiation-induced cell cycle arrest compromised by p21 deficiency
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“This arrest is mediated in large part by p21, a transcriptional target of the p53 protein which inhibits CDKs and prevents phosphorylation of the Rb protein, a requirement for S phase entry (2, 7).”
BackgroundInfluentialSelf-citationChen, P.-L., Scully, P., Shew, J.-Y., Wang, J. Y. J., & Lee, W.-H. (1989) · Cell · doi:10.1016/0092-8674(89)90517-5 · Cited by 952
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Wild-type p53 activates transcription in vitro
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Cell cycle dependent regulation of phosphorylation of the human retinoblastoma gene product
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Cited by
Genetic instabilities in human cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/25292 · Cited by 4,168
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222
Cell death by mitotic catastrophe: a molecular definition
Castedo, M., Perfettini, J.-L., Roumier, T., Andreau, K., Medema, R., & Kroemer, G. (2004) · Oncogene · doi:10.1038/sj.onc.1207528 · Cited by 1,269
Metadata
- Authors
- Lanni, J. S., & Jacks, T.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-02-01
- Volume
- 18
- Issue
- 2
- Pages
- 1055-1064
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2139718226
- Cited by
- 497
- References
- 9
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- green
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