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Publication : p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice.

First Author  Tan T Year  2002
Journal  Mol Cell Biol Volume  22
Issue  10 Pages  3247-54
PubMed ID  11971958 Mgi Jnum  J:76244
Mgi Id  MGI:2178902 Doi  10.1128/MCB.22.10.3247-3254.2002
Citation  Tan T, et al. (2002) p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice. Mol Cell Biol 22(10):3247-54
abstractText  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.
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