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XP-V patients are prone to the development of cancer in sun-exposed areas, and cells derived from XP-V patients demonstrate increased sensitivity to UV radiation and a higher mutation rate compared with wild-type cells. pol \u03b7 has been shown to replicate across a wide spectrum of DNA lesions introduced by environmental or chemotherapeutic agents, or during nucleotide starvation, suggesting that the biological roles for pol \u03b7 are not limited to repair of UV-damaged DNA. The high error rate of pol \u03b7 requires that its intracellular activity be tightly regulated. Here, we show that the phosphorylation of pol \u03b7 increased after UV irradiation, and that treatment with caffeine, siRNA against ATR, or an inhibitor of PKC (calphostin C), reduced the accumulation of pol \u03b7 at stalled replication forks after UV irradiation or treatment with cisplatin and gemcitabine. Site-specific mutagenesis (S587A and T617A) of pol \u03b7 at two putative PKC phosphorylation sites located in the protein\u2013protein interaction domain prevented nuclear foci formation induced by UV irradiation or treatment with gemcitabine\/cisplatin. In addition, XP-V cell lines stably expressing either the S587A or T617A mutant form of pol \u03b7 were more sensitive to UV radiation and gemcitabine\/cisplatin than control cells expressing wild-type pol \u03b7. These results suggest that phosphorylation is one mechanism by which the cellular activity of pol \u03b7 is regulated.<\/jats:p>","DOI":"10.1073\/pnas.0808589105","type":"journal-article","created":{"date-parts":[[2008,10,22]],"date-time":"2008-10-22T21:36:51Z","timestamp":1224711411000},"page":"16578-16583","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Human DNA polymerase \u03b7 activity and translocation is regulated by phosphorylation"],"prefix":"10.1073","volume":"105","author":[{"given":"Yih-wen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cleaver","sequence":"additional","affiliation":[{"name":"Dermatology and Pharmaceutical Chemistry, Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0808;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafer","family":"Hatahet","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Northwestern State University, Natchitoches, LA 71497;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Honkanen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of South Alabama, Mobile, AL 36688;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang-Yang","family":"Chang","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA 91010-3000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-ming","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,10,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1652"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2003.09.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/21447"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.12.3491"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/1.8.647"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.7.4276-4283.1993"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(02)00227-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-05-0118"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0818-9641.2004.01221.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.10.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210385"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35010014"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.187501"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600986"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00259-X"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510924103"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.020"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601123"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2847"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13945"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.2307\/3572829"},{"key":"e_1_3_3_22_2","first-page":"4237","article-title":"Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome","volume":"39","author":"Lehmann AR","year":"1979","unstructured":"AR Lehmann, S Kirk-Bell, L Mayne, Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome. 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