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Wild-type p53 is a cell cycle checkpoint determinant following irradiation.

Publication ,  Journal Article
Kuerbitz, SJ; Plunkett, BS; Walsh, WV; Kastan, MB
Published in: Proc Natl Acad Sci U S A
August 15, 1992

Cell cycle checkpoints appear to contribute to an increase in cell survival and a decrease in abnormal heritable genetic changes following exposure to DNA damaging agents. Though several radiation-sensitive yeast mutants have been identified, little is known about the genes that control these responses in mammalian cells. Recent studies from our laboratory have demonstrated a close correlation between expression of wild-type p53 genes in human hematopoietic cells and their ability to arrest in G1 phase after certain types of DNA damage. In the present study, this correlation was first generalized to nonhematopoietic mammalian cells as well. A cause and effect relationship between expression of wild-type p53 and the G1 arrest that occurs after gamma irradiation was then established by demonstrating (i) acquisition of the G1 arrest after gamma irradiation following transfection of wild-type p53 genes into cells lacking endogenous p53 genes and (ii) loss of the G1 arrest after irradiation following transfection of mutant p53 genes into cells with wild-type endogenous p53 genes. A defined role for p53 (the most commonly mutated gene in human cancers) in a physiologic pathway has, to our knowledge, not been reported previously. Furthermore, these experiments illustrate one way in which a mutant p53 gene product can function in a "dominant negative" manner. Participation of p53 in this pathway suggests a mechanism for the contribution of abnormalities in p53 to tumorigenesis and genetic instability and provides a useful model for studies of the molecular mechanisms of p53 involvement in controlling the cell cycle.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 15, 1992

Volume

89

Issue

16

Start / End Page

7491 / 7495

Location

United States

Related Subject Headings

  • Transfection
  • Skin
  • Repetitive Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Mammary Tumor Virus, Mouse
  • Leukemia, Promyelocytic, Acute
  • Humans
  • Genes, p53
  • Gene Expression
  • Gamma Rays
 

Citation

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Kuerbitz, S. J., Plunkett, B. S., Walsh, W. V., & Kastan, M. B. (1992). Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A, 89(16), 7491–7495. https://doi.org/10.1073/pnas.89.16.7491
Kuerbitz, S. J., B. S. Plunkett, W. V. Walsh, and M. B. Kastan. “Wild-type p53 is a cell cycle checkpoint determinant following irradiation.Proc Natl Acad Sci U S A 89, no. 16 (August 15, 1992): 7491–95. https://doi.org/10.1073/pnas.89.16.7491.
Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491–5.
Kuerbitz, S. J., et al. “Wild-type p53 is a cell cycle checkpoint determinant following irradiation.Proc Natl Acad Sci U S A, vol. 89, no. 16, Aug. 1992, pp. 7491–95. Pubmed, doi:10.1073/pnas.89.16.7491.
Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491–7495.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 15, 1992

Volume

89

Issue

16

Start / End Page

7491 / 7495

Location

United States

Related Subject Headings

  • Transfection
  • Skin
  • Repetitive Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Mammary Tumor Virus, Mouse
  • Leukemia, Promyelocytic, Acute
  • Humans
  • Genes, p53
  • Gene Expression
  • Gamma Rays