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Molecular and Cellular Biology, January 1999, p. 12-20, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

p53-Mediated Regulation of Proliferating Cell Nuclear Antigen Expression in Cells Exposed to Ionizing Radiation

Jin Xudagger and Gilbert F. Morris*

Programs in Molecular and Cellular Biology and Lung Biology, Department of Pathology, Tulane Cancer Center and Tulane/Xavier Center for Bioenvironmental Research, New Orleans, Louisiana 70112

Received 18 June 1998/Returned for modification 29 July 1998/Accepted 18 September 1998

The proliferating cell nuclear antigen (PCNA) is a highly conserved cellular protein that functions both in DNA replication and in DNA repair. Exposure of a rat embryo fibroblast cell line (CREF cells) to gamma  radiation induced simultaneous expression of PCNA with the p53 tumor suppressor protein and the cyclin-dependent kinase inhibitor p21WAF1/Cip1. PCNA mRNA levels transiently increased in serum-starved cells exposed to ionizing radiation, an observation suggesting that the radiation-associated increase in PCNA expression could be dissociated from cell cycle progression. Irradiation of CREF cells activated a transiently expressed PCNA promoter chloramphenicol acetyltransferase construct through p53 binding sequences via a mechanism blocked by a dominant negative mutant p53. Electrophoretic mobility shift assays with nuclear extracts prepared from irradiated CREF cells produced four p53-specific DNA-protein complexes with the PCNA p53 binding site. Addition of monoclonal antibody PAb421 (p53-specific) or AC238 (specific to the transcriptional coactivator p300/CREB binding protein) to the mobility shift assay distinguished different forms of p53 that changed in relative abundance with time after irradiation. These findings suggest a complex cellular response to DNA damage in which p53 transiently activates expression of PCNA for the purpose of limited DNA repair. In a population of nongrowing cells with diminished PCNA levels, this pathway may be crucial to survival following DNA damage.

* Corresponding author. Mailing address: Department of Pathology, SL-79, Tulane University Medical Center, 1430 Tulane Ave., New Orleans, LA 70112. Phone: (504) 585-6953. Fax: (504) 588-5707. E-mail: gmorris2{at}mailhost.tcs.tulane.edu.

dagger Present address: Department of Neurology, Harvard Medical School, The Children's Hospital, Boston, MA 02115.

Molecular and Cellular Biology, January 1999, p. 12-20, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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