{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:31:47Z","timestamp":1791106307141,"version":"4.1.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,24]]},"abstract":"<jats:p>\n                    Replication protein A (RPA) is a highly conserved single-stranded\n DNA-binding protein, required for cellular DNA replication, repair, and\n recombination. In human cells, RPA is phosphorylated during the S and\n G\n                    <jats:sub>2<\/jats:sub>\n                    phases of the cell cycle and also in response to\n ionizing or ultraviolet radiation.\n                    <jats:italic>Saccharomyces\n cerevisiae<\/jats:italic>\n                    exhibits a similar pattern of cell cycle-regulated\n RPA phosphorylation, and our studies indicate that the\n radiation-induced reactions occur in yeast as well. We have examined\n yeast RPA phosphorylation during the normal cell cycle and in response\n to environmental insult, and have demonstrated that the checkpoint gene\n                    <jats:italic>MEC1<\/jats:italic>\n                    is required for the reaction under all conditions\n tested. Through examination of several checkpoint mutants, we have\n placed RPA phosphorylation in a novel pathway of the DNA damage\n response.\n                    <jats:italic>MEC1<\/jats:italic>\n                    is similar in sequence to human ATM, the\n gene mutated in patients with ataxia-telangiectasia (A-T). A-T cells\n are deficient in multiple checkpoint pathways and are hypersensitive to\n killing by ionizing radiation. Because A-T cells exhibit a delay in\n ionizing radiation-induced RPA phosphorylation, our results indicate a\n functional similarity between\n                    <jats:italic>MEC1<\/jats:italic>\n                    and ATM, and suggest\n that RPA phosphorylation is involved in a conserved eukaryotic DNA\n damage-response pathway defective in A-T.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.26.15075","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"15075-15080","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["The ATM homologue\n                    <i>MEC1<\/i>\n                    is required for phosphorylation of replication protein A in\u2009yeast"],"prefix":"10.1073","volume":"93","author":[{"given":"George\u2009S.","family":"Brush","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight\u2009M.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Hieter","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas\u2009J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,24]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.7.1834"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.8.2523"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb02933.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39170-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39750-9"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99069-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53229-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07404.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.9.1589"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.4.6.968"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05277.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.12.7222-7231.1993"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06487.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12520"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7855601"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7855602"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90360-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3171"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90482-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7792600"},{"key":"e_1_3_2_21_2","first-page":"662","volume-title":"DNA Repair and Mutagenesis","author":"Friedberg E C","year":"1995","unstructured":"E C Friedberg, G C Walker, W Siede DNA Repair and Mutagenesis (Am. 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