{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:11:57Z","timestamp":1791216717072,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,2,17]]},"abstract":"<jats:p>\n                    Mutations in the human DDB2 gene give rise to xeroderma pigmentosum group E, a disease characterized by increased skin tumorigenesis in response to UV-irradiation. Cell strains derived from xeroderma pigmentosum group E individuals also have enhanced resistance to UV-irradiation due to decreased p53-mediated apoptosis. To further address the precise function(s) of DDB2 and the consequence of non-naturally occurring DDB2 mutations, we generated mice with a disruption of the gene. The mice exhibited significantly enhanced skin carcinogenesis in response to UV-irradiation, and cells from the DDB2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice were abnormally\n                    <jats:italic>resistant<\/jats:italic>\n                    to killing by the radiation and had diminished UV-induced, p53-mediated apoptosis. Notably, the cancer-prone phenotype and the resistance to cellular killing were not observed after exposure to the chemical carcinogen, 7,12-dimethylbenz[\n                    <jats:italic>a<\/jats:italic>\n                    ]anthracene (DMBA), to which mice carrying defective nucleotide excision repair genes respond with enhanced tumors and cell killing. Although cells from heterozygous DDB2\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice appeared normal, these mice had enhanced skin carcinogenesis after UV-irradiation, so that XP-E heterozygotes might be at risk for carcinogenesis. In sum, these results demonstrate that DDB2 is well conserved between humans and mice and functions as a tumor suppressor, at least in part, by controlling p53-mediated apoptosis after UV-irradiation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0306551101","type":"journal-article","created":{"date-parts":[[2004,2,17]],"date-time":"2004-02-17T15:32:02Z","timestamp":1077031922000},"page":"2052-2057","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen"],"prefix":"10.1073","volume":"101","author":[{"given":"Toshiki","family":"Itoh","sequence":"first","affiliation":[{"name":"Divisions of Biochemistry and Molecular Biology and Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202; and Department of Dermatology, Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Cado","sequence":"additional","affiliation":[{"name":"Divisions of Biochemistry and Molecular Biology and Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202; and Department of Dermatology, Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Kamide","sequence":"additional","affiliation":[{"name":"Divisions of Biochemistry and Molecular Biology and Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202; and Department of Dermatology, Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Linn","sequence":"additional","affiliation":[{"name":"Divisions of Biochemistry and Molecular Biology and Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202; and Department of Dermatology, Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,2,9]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"21422","volume":"272","year":"2000","unstructured":"Nichols, A. 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