Radiation-induced cell cycle arrest compromised by p21 deficiency

James Brugarolas, Chitra Chandrasekaran, Jeffrey I. Gordon, David Beach, Tyler Jacks, Gregory J. Hannon

Research output: Contribution to journalArticle

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Abstract

THE protein p21 is a dual inhibitor of cyclin-dependent kinases and proliferating-cell nuclear antigen (PCNA), both of which are required for passage through the cell cycle. The p21 gene is under the transcriptional control of p53, suggesting that p21 might promote p53-dependent cell cycle arrest or apoptosis. p21 has also been implicated in cell senescence and in cell-cycle withdrawal upon terminal differentiation. Here we investigate the role of p21 in these processes using chimaeric mice composed partly of p21(-/-) and partly of p21(+/+) cells. Immunohistochemical studies of the p21(+/+) and p21(-/-) components of adult small intestine indicated that deletion of p21 had no detectable effect on the migration-associated differentiation of the four principal intestinal epithelial cell lineages or on p53-dependent apoptosis following irradiation. However, p21(-/-) embryo fibroblasts are impaired in their ability to undergo G1 arrest following DNA damage.

Original languageEnglish (US)
Pages (from-to)552-557
Number of pages6
JournalNature
Volume377
Issue number6549
DOIs
StatePublished - Oct 12 1995

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Cell Cycle Checkpoints
Cell Cycle
Radiation
Apoptosis
Cyclin-Dependent Kinases
Cell Aging
Proliferating Cell Nuclear Antigen
Cell Lineage
DNA Damage
Small Intestine
Embryonic Structures
Fibroblasts
Epithelial Cells
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., & Hannon, G. J. (1995). Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature, 377(6549), 552-557. https://doi.org/10.1038/377552a0

Radiation-induced cell cycle arrest compromised by p21 deficiency. / Brugarolas, James; Chandrasekaran, Chitra; Gordon, Jeffrey I.; Beach, David; Jacks, Tyler; Hannon, Gregory J.

In: Nature, Vol. 377, No. 6549, 12.10.1995, p. 552-557.

Research output: Contribution to journalArticle

Brugarolas, J, Chandrasekaran, C, Gordon, JI, Beach, D, Jacks, T & Hannon, GJ 1995, 'Radiation-induced cell cycle arrest compromised by p21 deficiency', Nature, vol. 377, no. 6549, pp. 552-557. https://doi.org/10.1038/377552a0
Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995 Oct 12;377(6549):552-557. https://doi.org/10.1038/377552a0
Brugarolas, James ; Chandrasekaran, Chitra ; Gordon, Jeffrey I. ; Beach, David ; Jacks, Tyler ; Hannon, Gregory J. / Radiation-induced cell cycle arrest compromised by p21 deficiency. In: Nature. 1995 ; Vol. 377, No. 6549. pp. 552-557.
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