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Molecular and Cellular Biology, May 2002, p. 3247-3254, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3247-3254.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

p53 Binds and Activates the Xeroderma Pigmentosum DDB2 Gene in Humans but Not Mice

Thomas Tan and Gilbert Chu*

Departments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5151

Received 25 June 2001/ Returned for modification 20 August 2001/ Accepted 8 January 2002

The DDB2 gene, which is mutated in xeroderma pigmentosum group E, enhances global genomic repair of cyclobutane pyrimidine dimers and suppresses UV-induced mutagenesis. Because DDB2 transcription increases after DNA damage in a p53-dependent manner, we searched for and found a region in the human DDB2 gene that binds and responds transcriptionally to p53. The corresponding region in the mouse DDB2 gene shared significant sequence identity with the human gene but was deficient for p53 binding and transcriptional activation. Furthermore, when mouse cells were exposed to UV, DDB2 transcription remained unchanged, despite the accumulation of p53 protein. These results demonstrate direct activation of the human DDB2 gene by p53. They also explain an important difference in DNA repair between humans and mice and show how mouse models can be improved to better reflect cancer susceptibility in humans.

* Corresponding author. Mailing address: Division of Oncology, Stanford University School of Medicine, CCSR Room 1115, 269 Campus Dr., Stanford, CA 94305-5151. Phone: (650) 725-6442. Fax: (650) 725-1420. E-mail: chu{at}cmgm.stanford.edu.

Molecular and Cellular Biology, May 2002, p. 3247-3254, Vol. 22, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.10.3247-3254.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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