{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:41:25Z","timestamp":1792705285076,"version":"4.5.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,23]]},"abstract":"<jats:p>\n                    Cellular DNA double-strand break-repair pathways have evolved to protect the integrity of the genome from a continual barrage of potentially detrimental insults. Inherited mutations in genes that control this process result in an inability to properly repair DNA damage, ultimately leading to developmental defects and also cancer predisposition. Here, we describe a patient with a previously undescribed syndrome, which we have termed RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties), whose cells lack an ability to recruit 53BP1 to sites of DNA double-strand breaks. As a consequence, cells derived from this patient exhibit a hypersensitivity to ionizing radiation, cell cycle checkpoint abnormalities, and impaired end-joining in the recombined switch regions. Sequencing of\n                    <jats:italic>TP53BP1<\/jats:italic>\n                    and other genes known to regulate ionizing radiation-induced 53BP1 foci formation in this patient failed to detect any mutations. Therefore, these data indicate the existence of a DNA double-strand break-repair protein that functions upstream of 53BP1 and contributes to the normal development of the human immune system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0708408104","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T23:29:01Z","timestamp":1192577341000},"page":"16910-16915","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":175,"title":["RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling"],"prefix":"10.1073","volume":"104","author":[{"given":"Grant S.","family":"Stewart","sequence":"first","affiliation":[{"name":"*Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Stankovic","sequence":"additional","affiliation":[{"name":"*Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Byrd","sequence":"additional","affiliation":[{"name":"*Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wechsler","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Clare Hall Laboratories, London Research Institute, South Mimms, Hertfordshire EN6 3LD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward S.","family":"Miller","sequence":"additional","affiliation":[{"name":"*Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarn","family":"Huissoon","sequence":"additional","affiliation":[{"name":"Department of Immunology, Birmingham Heartlands Hospital, Birmingham, B9 5SS, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Drayson","sequence":"additional","affiliation":[{"name":"Division of Immunity and Infection, Birmingham University Medical School, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"West","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Clare Hall Laboratories, London Research Institute, South Mimms, Hertfordshire EN6 3LD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Elledge","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Malcolm R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"*Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham B15 2TT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,10,23]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldl006"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1395"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1067"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200403021"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/414660a"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040772"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122228699"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069398"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1004"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1216004"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076182"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01446"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.043"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb892"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.7.2556-2563.2003"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.4.1049-1059.2002"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1493"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.029"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01368"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182557299"},{"key":"e_1_3_5_21_2","first-page":"8586","volume":"63","author":"Mochan TA","year":"2003","unstructured":"TA Mochan, M Venere, RA DiTullio, TD Halazonetis Cancer Res 63, 8586\u20138591 (2003).","journal-title":"Cancer Res"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63672-3"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14066"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0708408104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T10:53:38Z","timestamp":1710240818000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.0708408104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10,23]]},"references-count":23,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2007,10,23]]}},"alternative-id":["10.1073\/pnas.0708408104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0708408104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10,23]]},"assertion":[{"value":"2007-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}