Work

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

Year: 2002

Type: article

Abstract: 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.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.22.10.3247-3254.2002

Authors: Thomas Tan, Gilbert Chu

Institutions: Stanford Medicine, Stanford University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Wellcome Trust, National Institutes of Health, National Institute of General Medical Sciences