{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:11:32Z","timestamp":1791162692726,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,12,20]]},"abstract":"<jats:p>\n                    In response to DNA damage, the Rad6\/Rad18 ubiquitin-conjugating complex monoubiquitinates the replication clamp proliferating cell nuclear antigen (PCNA) at Lys-164. Although ubiquitination of PCNA is recognized as an essential step in initiating postreplication repair, the mechanistic relevance of this modification has remained elusive. Here, we describe a robust\n                    <jats:italic>in vitro<\/jats:italic>\n                    system that ubiquitinates yeast PCNA specifically on Lys-164. Significantly, only those PCNA clamps that are appropriately loaded around effector DNA by its loader, replication factor C, are ubiquitinated. This observation suggests that,\n                    <jats:italic>in vitro<\/jats:italic>\n                    , only PCNA present at stalled replication forks is ubiquitinated. Ubiquitinated PCNA displays the same replicative functions as unmodified PCNA. These functions include loading onto DNA by replication factor C, as well as Okazaki fragment synthesis and maturation by the PCNA-coordinated actions of DNA polymerase \u03b4, the flap endonuclease FEN1, and DNA ligase I. However, whereas the activity of DNA polymerase \u03b6 remains unaffected by ubiquitination of PCNA, ubiquitinated PCNA specifically activates two key enzymes in translesion synthesis: DNA polymerase \u03b7, the yeast\n                    <jats:italic>Xeroderma pigmentosum<\/jats:italic>\n                    ortholog, and Rev1, a deoxycytidyl transferase that functions in organizing the mutagenic DNA replication machinery. We propose that ubiquitination of PCNA increases its functionality as a sliding clamp to promote mutagenic DNA replication.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0505949102","type":"journal-article","created":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T21:03:36Z","timestamp":1134421416000},"page":"18361-18366","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":208,"title":["Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases \u03b7 and REV1"],"prefix":"10.1073","volume":"102","author":[{"given":"Parie","family":"Garg","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Burgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,12,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00991"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.06.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01965"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.10.4267-4274.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133250"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2003.08.026"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00367-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400006200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00306-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5404.1001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.12.3491"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.103.021675"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5268.1646"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/382729a0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112146200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh710"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.034611"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2005.03.005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1009802"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.03.032"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00259-X"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600383"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00319-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261560798"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.3.784-791.2002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406511200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500173200"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209801200"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.11.6367"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.8.4420"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.2.861"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.37.23360"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4586"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.7.811"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9676"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011743200"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409230590935433"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.31.19756"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1016-8478(23)17076-2","volume":"12","year":"2001","unstructured":"Hubscher, U. & Seo, Y. 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