Cited by 167DNA Repair MechanismsCancer-related Molecular PathwaysGenetic factors in colorectal cancer

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

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Tan, Thomas, Chu, Gilbert·2002·Molecular and Cellular Biology

DOI 10.1128/mcb.22.10.3247-3254.2002PMC PMC133779

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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.

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Authors: Tan, T., & Chu, G.
Affiliations: Stanford Medicine (US)
Corresponding author: Chu, Gilbert
ORCID: Tan, Thomas
Chu, Gilbert
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2002-05
Volume: 22
Issue: 10
Pages: 3247-3254
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.22.10.3247-3254.2002
PMC: PMC133779
OpenAlex: W2147640875
Cited by: 167
References: 38
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 5
FWCI: 3.02
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
National Institutes of Health
National Institute of General Medical Sciences (T32GM007276, GMO7276)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: p53, transcriptional activation, p53 binding sites, cyclobutane pyrimidine dimers, UV mutagenesis, DNA damage response, mouse tumor model, DNA repair
MeSH terms: Animals, Base Sequence, Cell Line, DNA Repair, DNA-Binding Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Transcription, Genetic, Ultraviolet Rays, Xeroderma Pigmentosum, Tumor Suppressor Protein p53, Genes, Reporter, Response Elements, Mice

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

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