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PMID: 9822382 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Requirement for p53 and p21 to sustain G2 arrest after DNA damage.

Science (New York, N.Y.) ·Vol. 282 ·No. 5393 ·1998-11-20 ·Pages 1497-501

Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B

Abstract

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.

MeSH Terms

Apoptosis CDC2 Protein Kinase/antagonists & inhibitors,metabolism Cell Line Cyclin B/metabolism Cyclin B1 Cyclin-Dependent Kinase Inhibitor p21 Cyclins/genetics,physiology DNA/analysis DNA Damage G2 Phase/drug effects Gamma Rays Gene Expression Regulation Genes, p53 Humans Mitosis Mutation Nocodazole/pharmacology Tumor Cells, Cultured Tumor Suppressor Protein p53/physiology

Chemicals

CCNB1 protein, human CDKN1A protein, human Cyclin B Cyclin B1 Cyclin-Dependent Kinase Inhibitor p21 Cyclins Tumor Suppressor Protein p53 DNA CDC2 Protein Kinase Nocodazole

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Bunz F

The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.

Dutriaux A

Lengauer C

Waldman T

Zhou S

Brown J P

Sedivy J M

Kinzler K W

Vogelstein B

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.282.5393.1497

Published

1998-11-20

Pages

1497-501

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NCI NIH HHS · CA 43460 · United States

NCI NIH HHS · CA 57345 · United States

NCI NIH HHS · CA 62924 · United States

External Links

PubMed source DOI: 10.1126/science.282.5393.1497 View journal details

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Requirement for p53 and p21 to sustain G2 arrest after DNA damage.

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