{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:16:19Z","timestamp":1791018979532,"version":"4.1.0"},"reference-count":67,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,8]]},"abstract":"<jats:p>\n                    UV-induced replication arrest in the xeroderma pigmentosum\n variant (XPV) but not in normal cells leads to an accumulation of the\n Mre11\/Rad50\/Nbs1 complex and phosphorylated histone H2AX\n (\u03b3-H2AX) in large nuclear foci at sites of stalled replication\n forks. These complexes have been shown to signal the presence of DNA\n damage, in particular, double-strand breaks (DSBs). This finding\n suggests that UV damage leads to the formation of DSBs during the\n course of replication arrest. After UV irradiation, XPV cells showed a\n fluence-dependent increase in the yield of \u03b3-H2AX foci that\n paralleled the production of Mre11 foci. The percentage of\n foci-positive cells increased rapidly (10\u201315%) up to fluences of 10\n J\u22c5m\n                    <jats:sup>\u22122<\/jats:sup>\n                    before saturating at higher fluences.\n Frequencies of \u03b3-H2AX and Mre11 foci both reached maxima at 4 h\n after UV irradiation. This pattern contrasts sharply to the\n situation observed after x-irradiation, where peak levels of\n \u03b3-H2AX foci were found to precede the formation of Mre11 foci by\n several hours. The nuclear distributions of \u03b3-H2AX and Mre11 were\n found to colocalize spatially after UV- but not x-irradiation.\n UV-irradiated XPV cells showed a one-to-one correspondence between\n Mre11 and \u03b3-H2AX foci-positive cells. These results show that XPV\n cells develop DNA DSBs during the course of UV-induced replication\n arrest. These UV-induced foci occur in cells that are unable to carry\n out efficient bypass replication of UV damage and may contribute to\n further genetic variation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.231611798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"233-238","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":185,"title":["UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, \u03b3-H2AX formation, and Mre11 relocalization"],"prefix":"10.1073","volume":"99","author":[{"given":"Charles L.","family":"Limoli","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of California, San\r Francisco, CA 94103-0806; Laboratory of Molecular\r Pharmacology, National Institutes of Health, Bethesda, MD 20892; and\r Department of Dermatology, Cancer Center, University of\r California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Giedzinski","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, San\r Francisco, CA 94103-0806; Laboratory of Molecular\r Pharmacology, National Institutes of Health, Bethesda, MD 20892; and\r Department of Dermatology, Cancer Center, University of\r California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Bonner","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, San\r Francisco, CA 94103-0806; Laboratory of Molecular\r Pharmacology, National Institutes of Health, Bethesda, MD 20892; and\r Department of Dermatology, Cancer Center, University of\r California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cleaver","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, San\r Francisco, CA 94103-0806; Laboratory of Molecular\r Pharmacology, National Institutes of Health, Bethesda, MD 20892; and\r Department of Dermatology, Cancer Center, University of\r California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.18.2956"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00220-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.914401"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2307\/3574254"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(81)90297-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/365022a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12538913"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2787(79)90193-X"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/7.7.1901"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.263"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/21447"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13945"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2847"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.130182897"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1217"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.10.6087"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5363.590"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81175-7"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35007091"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013089"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013083"},{"key":"e_1_3_3_22_2","volume-title":"DNA Repair and Mutagenesis","author":"Friedberg E C","year":"1995","unstructured":"E C Friedberg, G Walker, W Siede DNA Repair and Mutagenesis (Am. Soc. Microbiol., Washington, DC, 1995)."},{"key":"e_1_3_3_23_2","first-page":"1102","volume":"59","author":"Cleaver J E","year":"1999","unstructured":"J E Cleaver, V Afzal, L Feeney, M McDowell, W Sadinski, J P G Volpe, D B Busch, D M Coleman, D W Ziffer, Y J Yu, et al. Cancer Res 59, 1102\u20131108 (1999).","journal-title":"Cancer Res"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.1.93"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.13.3398"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.2.430"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/144.3.935"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90105-1"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100448097"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd004"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.13.3428"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.5166"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(00)00052-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4564"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/35087607"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/35087613"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5459.1824"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/35071124"},{"key":"e_1_3_3_39_2","unstructured":"Ward I. M. & Chen J. (October 22 2001) J.\n Biol. Chem. 10.1074\/jbc.C100569200."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5858"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.5.905"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.1.281-288.2001"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.23.6619"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.212"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.2307\/3578455"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9390"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5498.1962"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00610-2"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/85830"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.2307\/3578093"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1674"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1677"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.2.152"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7303"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111125998"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.851000"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.38.23896"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.5.1199"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.9.5315-5322.1993"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/153.4.1873"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110144297"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80097-0"},{"key":"e_1_3_3_63_2","first-page":"1043","volume":"278","author":"Fearon E R","year":"1997","unstructured":"E R Fearon Nature (London) 278, 1043\u20131049 (1997).","journal-title":"Nature (London)"},{"key":"e_1_3_3_64_2","first-page":"245","volume-title":"The Genetic Basis of Human Cancer","author":"Bootsma D","year":"1998","unstructured":"D Bootsma, K H Kraemer, J E Cleaver, J H J Hoeijmakers The Genetic Basis of Human Cancer, eds B Vogelstein, K W Kinzler (McGraw\u2013Hill, New York), pp. 245\u2013274 (1998)."},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.53.37538"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01571-1"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161004898"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.231611798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:26:48Z","timestamp":1649842008000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.231611798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,26]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1,8]]}},"alternative-id":["10.1073\/pnas.231611798"],"URL":"https:\/\/doi.org\/10.1073\/pnas.231611798","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,12,26]]},"assertion":[{"value":"2001-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}