{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:41:01Z","timestamp":1791297661853,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,11,14]]},"abstract":"<jats:p>\n                    Eukaryotic cells respond to a variety of DNA insults by triggering a common signal transduction cascade, known as checkpoint response, which temporarily halts cell-cycle progression. Although the main players involved in the cascade have been identified, there is still uncertainty about the nature of the structures that activate these surveillance mechanisms. To understand the role of nucleotide excision repair (NER) in checkpoint activation, we analyzed the UV-induced phosphorylation of the key checkpoint proteins Chk1 and p53, in primary fibroblasts from patients with xeroderma pigmentosum (XP), Cockayne syndrome (CS), trichothiodystrophy (TTD), or UV light-sensitive syndrome. These disorders are due to defects in transcription-coupled NER (TC-NER) and\/or global genome NER (GG-NER), the NER subpathways repairing the transcribed strand of active genes or the rest of the genome, respectively. We show here that in G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    and G\n                    <jats:sub>2<\/jats:sub>\n                    \/M phases of the cell cycle, triggering of the DNA damage cascade requires recognition and processing of the lesions by the GG-NER. Loss of TC-NER does not affect checkpoint activation. Mutations in\n                    <jats:italic>XPD<\/jats:italic>\n                    ,\n                    <jats:italic>XPB<\/jats:italic>\n                    , and in\n                    <jats:italic>TTDA<\/jats:italic>\n                    , encoding subunits of the TFIIH complex, involved in both transcription and NER, impair checkpoint triggering. The only exception is represented by mutations in\n                    <jats:italic>XPD<\/jats:italic>\n                    , resulting in combined features of XP and CS (XP\/CS) that lead to activation of the checkpoint cascade after UV radiation. Inhibition of RNA polymerase II transcription significantly reduces the phosphorylation of key checkpoint factors in XP\/CS fibroblasts on exposure to UV damage.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0605446103","type":"journal-article","created":{"date-parts":[[2006,11,6]],"date-time":"2006-11-06T20:54:23Z","timestamp":1162846463000},"page":"17325-17330","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["DNA nucleotide excision repair-dependent signaling to checkpoint activation"],"prefix":"10.1073","volume":"103","author":[{"given":"Federica","family":"Marini","sequence":"first","affiliation":[{"name":"*Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit\u00e1 degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Nardo","sequence":"additional","affiliation":[{"name":"Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Giannattasio","sequence":"additional","affiliation":[{"name":"*Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit\u00e1 degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Minuzzo","sequence":"additional","affiliation":[{"name":"*Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit\u00e1 degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miria","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Plevani","sequence":"additional","affiliation":[{"name":"*Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit\u00e1 degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Muzi","family":"Falconi","sequence":"additional","affiliation":[{"name":"*Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit\u00e1 degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,11,14]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083430"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1316905"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.1.39-49.2006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","unstructured":"EC Friedberg GC Walker W Siede RD Wood RA 1Schultz T Ellenberger DNA Repair and Mutagenesis.  (Am Soc Microbiol Press Washington DC 2005).","DOI":"10.1128\/9781555816704"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2005.03.017"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600051"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1129"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603779103"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300554200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601123"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2744(200009)29:1<17::AID-MC3>3.0.CO;2-E"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2005.12.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.935"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203583"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600849"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0921-8777(94)90068-X"},{"key":"e_1_3_4_18_2","first-page":"1974","volume":"60","author":"Chavanne F","year":"2000","unstructured":"F Chavanne, BC Broughton, D Pietra, T Nardo, A Browitt, AR Lehmann, M Stefanini Cancer Res 60, 1974\u20131982 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80132-X"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg174"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.424"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01673.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(97)00031-1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.859501"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-36802-7_3"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8658"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/302063"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1387"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.6.1101"},{"key":"e_1_3_4_30_2","first-page":"191","volume":"54","author":"Vermeulen W","year":"1994","unstructured":"W Vermeulen, RJ Scott, S Rodgers, HJ Muller, J Cole, CF Arlett, WJ Kleijer, D Bootsma, JHJ Hoeijmakers, G Weeda Am J Hum Genet 54, 191\u2013200 (1994).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.10.024"},{"key":"e_1_3_4_32_2","first-page":"431","volume":"60","author":"Berneburg M","year":"2000","unstructured":"M Berneburg, PH Clingen, SA Harcourt, JE Lowe, EM Taylor, MH Green, J Krutmann, CF Arlett, AR Lehmann Cancer Res 60, 431\u2013438 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.18.8368-8378.2005"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0605446103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:45:35Z","timestamp":1649778335000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0605446103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,14]]},"references-count":33,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2006,11,14]]}},"alternative-id":["10.1073\/pnas.0605446103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0605446103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,14]]},"assertion":[{"value":"2006-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}