{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:49:39Z","timestamp":1791002979614,"version":"4.1.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,12,21]]},"abstract":"<jats:p>\n                    After exposure to DNA-damaging agents, the p53 tumor suppressor protects against neoplastic transformation by inducing growth arrest and apoptosis. A series of investigations has also demonstrated that, in UV-exposed cells, p53 regulates the removal of DNA photoproducts from the genome overall (global nucleotide excision repair), but does not participate in an overlapping pathway that removes damage specifically from the transcribed strand of active genes (transcription-coupled nucleotide excision repair). Here, the highly sensitive ligation-mediated PCR was employed to quantify, at nucleotide resolution, the repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in genetically p53-deficient Li\u2013Fraumeni skin fibroblasts, as well as in human lung fibroblasts expressing the human papillomavirus (HPV) E6 oncoprotein that functionally inactivates p53. Lung fibroblasts expressing the HPV E7 gene product, which similarly inactivates the retinoblastoma tumor-suppressor protein (pRb), were also investigated. pRb acts downstream of p53 to mediate G\n                    <jats:sub>1<\/jats:sub>\n                    arrest, but has no demonstrated role in DNA repair. Relative to normal cells, HPV E6-expressing lung fibroblasts and Li\u2013Fraumeni skin fibroblasts each manifested defective CPD repair along both the transcribed and nontranscribed strands of the p53 and\/or c-\n                    <jats:italic>jun<\/jats:italic>\n                    loci. HPV E7-expressing lung fibroblasts also exhibited reduced CPD removal, but only along the nontranscribed strand. Our results provide striking evidence that transcription-coupled repair, in addition to global repair, are p53-dependent in UV-exposed human fibroblasts. Moreover, the observed DNA-repair defect in HPV E7-expressing cells reveals a function for this oncoprotein in HPV-mediated carcinogenesis, and may suggest a role for pRb in global nucleotide excision repair.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.26.15038","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"15038-15043","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["Human cells compromised for p53 function exhibit defective global and transcription-coupled nucleotide excision repair, whereas cells compromised for pRb function are defective only in global repair"],"prefix":"10.1073","volume":"96","author":[{"given":"Jean-Philippe","family":"Therrien","sequence":"first","affiliation":[{"name":"Division of Pathology, Department of Medical Biology, Faculty of Medicine, Laval University and Unit\u00e9 de Recherche en G\u00e9n\u00e9tique Humaine et Mol\u00e9culaire, Research Centre, Pavillon St-Fran\u00e7ois d'Assise, Centre Hospitalier Universitaire de Qu\u00e9bec, PQ, Canada G1L 3L5; and Department of Microbiology and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al and Centre de Recherche Guy-Bernier, H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, PQ, Canada H1T 2M4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gen","family":"Drouin","sequence":"additional","affiliation":[{"name":"Division of Pathology, Department of Medical Biology, Faculty of Medicine, Laval University and Unit\u00e9 de Recherche en G\u00e9n\u00e9tique Humaine et Mol\u00e9culaire, Research Centre, Pavillon St-Fran\u00e7ois d'Assise, Centre Hospitalier Universitaire de Qu\u00e9bec, PQ, Canada G1L 3L5; and Department of Microbiology and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al and Centre de Recherche Guy-Bernier, H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, PQ, Canada H1T 2M4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Baril","sequence":"additional","affiliation":[{"name":"Division of Pathology, Department of Medical Biology, Faculty of Medicine, Laval University and Unit\u00e9 de Recherche en G\u00e9n\u00e9tique Humaine et Mol\u00e9culaire, Research Centre, Pavillon St-Fran\u00e7ois d'Assise, Centre Hospitalier Universitaire de Qu\u00e9bec, PQ, Canada G1L 3L5; and Department of Microbiology and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al and Centre de Recherche Guy-Bernier, H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, PQ, Canada H1T 2M4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot A.","family":"Drobetsky","sequence":"additional","affiliation":[{"name":"Division of Pathology, Department of Medical Biology, Faculty of Medicine, Laval University and Unit\u00e9 de Recherche en G\u00e9n\u00e9tique Humaine et Mol\u00e9culaire, Research Centre, Pavillon St-Fran\u00e7ois d'Assise, Centre Hospitalier Universitaire de Qu\u00e9bec, PQ, Canada G1L 3L5; and Department of Microbiology and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al and Centre de Recherche Guy-Bernier, H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, PQ, Canada H1T 2M4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,12,21]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"435","volume":"104","author":"Harris C C","year":"1996","unstructured":"C C Harris Environ Health Perspect 104, 435\u2013439 (1996).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_3_2_2","first-page":"197","volume":"1198","author":"Malkin D","year":"1994","unstructured":"D Malkin Biochim Biophys Acta 1198, 197\u2013213 (1994).","journal-title":"Biochim Biophys 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