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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,5,5]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>DNA replication accuracy is critical for genetic stability and is ensured by high-fidelity replicative DNA polymerases and the mismatch repair (MMR) system, both of which are regulated by the proliferating cell nuclear antigen (PCNA). Dysfunction of either system leads to genome instability and cancer development. Interestingly, many types of cancers have no obvious defects in either system, but they display increased mutation frequency during development. The underlying mechanism is unknown. We demonstrate here that PCNA tyrosine phosphorylation by epidermal growth factor receptor (EGFR) inhibits MMR and promotes misincorporation during DNA synthesis. This study therefore discovers a novel mechanism promoting genome instability and explains why progression of many cancer types is associated with EGFR overexpression and\/or activation.<\/jats:p>","DOI":"10.1073\/pnas.1417711112","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T05:46:36Z","timestamp":1427867196000},"page":"5667-5672","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis"],"prefix":"10.1073","volume":"112","author":[{"given":"Janice","family":"Ortega","sequence":"first","affiliation":[{"name":"Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie Y.","family":"Li","sequence":"additional","affiliation":[{"name":"Paul Laurence Dunbar High School, Lexington, KY 40513; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536;"},{"name":"Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536;"},{"name":"Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,3,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.12.1433"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.000533"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133243"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.115"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5837"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318971110"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.039"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200627200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.5.1173"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81323-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.04.034"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.027"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.7.2037-2046.2002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(95)80055-7"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6870"},{"key":"e_1_3_3_16_2","first-page":"808","article-title":"Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines","volume":"57","author":"Kane MF","year":"1997","unstructured":"MF Kane, , Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. 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