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We now have identified that XPV cells make use of a homologous recombination pathway involving the hMre11\/hRad50\/Nbs1 protein complex, but not the Rad51 recombination pathway. The hMre11 complexes form at arrested replication forks, in association with proliferating cell nuclear antigen. In x-ray-damaged cells, in contrast, there is no association between hMre11 and proliferating cell nuclear antigen. This recombination pathway assumes greater importance in transformed XPV cells that lack a functional p53 pathway and can be detected at lower frequencies in excision-defective XPA fibroblasts and normal cells. DNA replication arrest after UV damage, and the associated S phase checkpoint, is therefore a complex process that can recruit a recombination pathway that has a primary role in repair of double-strand breaks from x-rays. The symptoms of elevated solar carcinogenesis in XPV patients therefore may be associated with increased genomic rearrangements that result from double-strand breakage and rejoining in cells of the skin in which p53 is inactivated by UV-induced mutations.<\/jats:p>","DOI":"10.1073\/pnas.130182897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"7939-7946","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":78,"title":["Polymerase \u03b7 deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair"],"prefix":"10.1073","volume":"97","author":[{"given":"Charles L.","family":"Limoli","sequence":"first","affiliation":[{"name":"Departments of Radiology and Radiation Oncology, University of California, San Francisco, CA 94103-0806; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201-1559; and Department of Dermatology, Cancer Center, University of California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Giedzinski","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Radiation Oncology, University of California, San Francisco, CA 94103-0806; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201-1559; and Department of Dermatology, Cancer Center, University of California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Radiation Oncology, University of California, San Francisco, CA 94103-0806; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201-1559; and Department of Dermatology, Cancer Center, University of California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cleaver","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Radiation Oncology, University of California, San Francisco, CA 94103-0806; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201-1559; and Department of Dermatology, Cancer Center, University of California, San Francisco, CA 94143-0808"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,6,20]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"4393","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Cleaver J E","year":"1995","unstructured":"J E Cleaver, K H Kraemer The Metabolic and Molecular Bases of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw\u2013Hill, New York) III, 4393\u20134419 (1995)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/5.4.511"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1994.01690080084012"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1992.01680190089011"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12538913"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131646"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/261593a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(76)90272-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12371686"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7810"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.7.4276-4283.1993"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.263"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/21447"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7447"},{"key":"e_1_3_3_15_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. 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