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Molecular and Cellular Biology, November 2003, p. 7540-7553, Vol. 23, No. 21
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.21.7540-7553.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Impaired Regulation of Tumor Suppressor p53 Caused by Mutations in the Xeroderma Pigmentosum DDB2 Gene: Mutual Regulatory Interactions between p48^DDB2 and p53

Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202,¹ UCSF Cancer Center and Department of Dermatology, University of California, San Francisco, California 94143-0808²

Received 19 May 2003/ Returned for modification 25 June 2003/ Accepted 29 July 2003

Tumor suppressor p53 controls cell cycle progression and apoptosis following DNA damage, thus minimizing carcinogenesis. Mutations in the human DDB2 gene generate the E subgroup of xeroderma pigmentosum (XP-E). We report here that XP-E strains are defective in UV irradiation-induced apoptosis due to severely reduced basal and UV-induced p53 levels. These defects are restored by infection with a p53 cDNA expression construct or with a DDB2 expression construct if and only if it contains intron 4, which includes a nonmutated p53 consensus-binding site. We propose that both before and after UV irradiation, DDB2 directly regulates p53 levels, while DDB2 expression is itself regulated by p53.

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