{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:18:38Z","timestamp":1793247518811,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,7,14]]},"abstract":"<jats:p>\n                    Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase \u03b7, the\n                    <jats:italic>POLH<\/jats:italic>\n                    gene product. A deficiency in DNA polymerase \u03b7 due to germ-line mutations in\n                    <jats:italic>POLH<\/jats:italic>\n                    causes the hereditary disease xeroderma pigmentosum variant (\n                    <jats:italic>XPV<\/jats:italic>\n                    ), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer.\n                    <jats:italic>XPV<\/jats:italic>\n                    cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase \u03b6 cooperates with DNA polymerases \u03ba and \u03b9 to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases \u03b6 and \u03ba, but not \u03b9, protect\n                    <jats:italic>XPV<\/jats:italic>\n                    cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0812548106","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T21:42:29Z","timestamp":1246311749000},"page":"11552-11557","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":120,"title":["DNA polymerase \u03b6 cooperates with polymerases \u03ba and \u03b9 in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients"],"prefix":"10.1073","volume":"106","author":[{"given":"Omer","family":"Ziv","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Geacintov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, New York University, New York, NY 10003-5180; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai, 980-8575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aobaku, Sendai, 980-8575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Livneh","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,7,14]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"DNA Repair and Mutagenesis","author":"Friedberg EC","year":"2006","unstructured":"EC Friedberg, et al. DNA Repair and Mutagenesis (ASM Press, 2nd edition, Washington DC, 2006).","edition":"2"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100019200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133250"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704219104"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.117"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00991"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00259-X"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.022"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209315"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/21447"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.263"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/261593a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605247103"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3073"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.05.012"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409155200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.281"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2006.07.002"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.06.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5404.1001"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.13.1589"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.210"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1417"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406070200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-7864(03)00094-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/35023030"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032594399"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.034611"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2982"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.031"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg308"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6876"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(02)00253-1"},{"key":"e_1_3_3_34_2","first-page":"836","article-title":"Decreased Frequency and Highly Aberrant Spectrum of Ultraviolet-Induced Mutations in the hprt Gene of Mouse Fibroblasts Expressing Antisense RNA to DNA Polymerase \u03b6","volume":"1","author":"Diaz M","year":"2003","unstructured":"M Diaz, et al., Decreased Frequency and Highly Aberrant Spectrum of Ultraviolet-Induced Mutations in the hprt Gene of Mouse Fibroblasts Expressing Antisense RNA to DNA Polymerase \u03b6. Mol Cancer Res 1, 836\u2013847 (2003).","journal-title":"Mol Cancer Res"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.01.003"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.8919"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.45.31763"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222377899"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01919"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb792"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600849"},{"key":"e_1_3_3_42_2","article-title":"DNA polymerase \u03ba from Trypanosoma cruzi localizes to the mitochondria, bypasses 8-oxoguanine, and performs DNA synthesis in a recombination intermediate","author":"Rajao MA","year":"2008","unstructured":"MA Rajao, et al., DNA polymerase \u03ba from Trypanosoma cruzi localizes to the mitochondria, bypasses 8-oxoguanine, and performs DNA synthesis in a recombination intermediate. Mol Microbiol, In press. (2008).","journal-title":"Mol Microbiol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.10.016"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.10.001"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi982599"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0812548106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:30:42Z","timestamp":1649784642000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0812548106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,14]]},"references-count":45,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2009,7,14]]}},"alternative-id":["10.1073\/pnas.0812548106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0812548106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,14]]},"assertion":[{"value":"2008-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-07-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}