{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:50:10Z","timestamp":1790941810123,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,10,10]]},"abstract":"<jats:p>\n                    Nucleotide excision repair (NER), apoptosis, and cell-cycle\n regulation are major defense mechanisms against the carcinogenic\n effects of UVB light. NER eliminates UVB-induced DNA photolesions via\n two subpathways: global genome repair (GGR) and transcription-coupled\n repair (TCR). Defects in NER result in the human disorders xeroderma\n pigmentosum (XP) and Cockayne syndrome (CS), displaying severe UV\n sensitivity and in the case of XP, cancer proneness. We investigated\n the impact of deficiencies in NER subpathways on apoptosis,\n hyperplasia, and cell cycle progression in the epidermis of UVB-exposed\n CS group B (\n                    <jats:italic>Csb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice (no TCR), XP\n group C (\n                    <jats:italic>Xpc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice (no GGR), and XP\n group A (\n                    <jats:italic>Xpa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice (no TCR and no\n GGR). On UVB treatment (250 J\/m\n                    <jats:sup>2<\/jats:sup>\n                    ),\n                    <jats:italic>Xpa<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Csb<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice revealed an extensive\n apoptotic response in the skin, a blockage of cell cycle\n progression of epidermal cells, and strong hyperplasia. Interestingly,\n the absence of this apoptotic response in the skin of wild-type\n and\n                    <jats:italic>Xpc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice coincided with the\n ability of epidermal cells to enter the S phase. However, only\n epidermal cells of\n                    <jats:italic>Xpc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice\n subsequently became arrested in the G\n                    <jats:sub>2<\/jats:sub>\n                    phase. Our data\n demonstrate that TCR (and\/or restoration of UVB-inhibited\n transcription) enables damaged cells to progress through S phase and\n prevents the induction of apoptosis and hyperplasia.\n G\n                    <jats:sub>2<\/jats:sub>\n                    arrest is manifest only under conditions of proficient\n TCR in combination with deficient GGR, indicating that epidermal cells\n become arrested in the G\n                    <jats:sub>2<\/jats:sub>\n                    phase as a result of persisting\n damage in their genome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.200226697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"11268-11273","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":77,"title":["Differential role of transcription-coupled repair in UVB-induced G\n                    <sub>2<\/sub>\n                    arrest and apoptosis in mouse epidermis"],"prefix":"10.1073","volume":"97","author":[{"given":"Marijke","family":"van Oosten","sequence":"first","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heggert","family":"Rebel","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errol C.","family":"Friedberg","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"van Steeg","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijsbertus T. J.","family":"van der Horst","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk J.","family":"van Kranen","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Westerman","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert A.","family":"van Zeeland","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon H. F.","family":"Mullenders","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"de Gruijl","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics and Chemical Mutagenesis MGC,\r Leiden University Medical Center, 2333 AL Leiden, The Netherlands;\r Department of Dermatology, University of Utrecht,\r Utrecht, The Netherlands; Laboratory of Molecular\r Pathology, Department of Pathology, University of Texas Southwestern\r Medical Center, Dallas, TX 75235; Laboratory of Health\r Effects Research, National Institute of Public Health and\r Environment, Bilthoven, The Netherlands; Department of\r Cell Biology and Genetics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,9,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90150-3"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90151-6"},{"key":"e_1_3_3_3_2","first-page":"2949","volume-title":"The Metabolic Basis of Inherited Disease","author":"Cleaver J E","year":"1989","unstructured":"J E Cleaver, K H Kraemer The Metabolic Basis of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw\u2013Hill, New York), pp. 2949\u20132971 (1989)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(93)90026-C"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/5.4.511"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1987.01660260111026"},{"key":"e_1_3_3_7_2","first-page":"137","volume":"1242","author":"Ma L","year":"1995","unstructured":"L Ma, J H J Hoeijmakers, A J van der Eb Biochim Biophys Acta 1242, 137\u2013164 (1995).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_8_2","volume-title":"DNA Repair and Mutagenesis","author":"Friedberg E C","year":"1995","unstructured":"E C Friedberg, G C Walker, W Siede DNA Repair and Mutagenesis (Am. 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