{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:06:41Z","timestamp":1790024801325,"version":"4.0.1"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1ZIABC012071"],"award-info":[{"award-number":["1ZIABC012071"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>Peroxiredoxin 1 (PRDX1) is a highly conserved, thiol-dependent peroxidase that rapidly scavenges reactive oxygen species to modulate redox signaling. PRDX1-null mice exhibited genomic instability, shortened life span, and accelerated tumorigenesis, including development of lymphomas, sarcomas, and carcinomas. Despite extensive characterization of these phenotypes, the molecular mechanism by which PRDX1 loss causes genomic instability remains poorly understood. Here, we show that PRDX1 deficiency alters nucleolar morphology, impairs RNA polymerase I (POL-I)\u2013dependent transcription of pre\u2013ribosomal RNAs, and triggers nucleolar genomic instability. This oxidative stress\u2013induced nucleolar dysfunction promotes the stability of secondary DNA structures, such as RNA-DNA hybrids and G-quadruplex DNA, contributing to nucleolar genomic instability. We demonstrate that PRDX1 loss reduces nascent ribosomal RNA (rRNA) levels and impairs rRNA processing, further affecting ribosome biogenesis. Mechanistically, we established that PRDX1 loss triggers activation of the nucleolar DNA damage response characterized by activation of the DNA repair kinase ATM and elevated TCOF1 within the nucleolus. In addition, we observed recruitment of the MRE11-RAD50-NBS1 (MRN) complex subunit NBS1 to ribosomal DNA (rDNA) loci and this was further increased under oxidative stress. NBS1 accumulation correlates with the repression of rDNA transcription by POL-I, potentially delaying rRNA synthesis, and safeguarding the nucleolar genome from further oxidative damage. Collectively, these findings uncover a previously unrecognized, but critical role, for PRDX1 in maintaining nucleolar integrity and ribosomal biogenesis through redox-dependent regulation of rDNA transcription and processing machinery.<\/jats:p>","DOI":"10.1126\/sciadv.aed4161","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:47Z","timestamp":1788976727000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2769-3576","authenticated-orcid":true,"given":"Vaibhavi","family":"Gujar","sequence":"first","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Furusawa","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-3650","authenticated-orcid":true,"given":"Shalu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frimpong","family":"Boateng","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojian","family":"Li","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-5958","authenticated-orcid":true,"given":"Cyrinne","family":"Achour","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-4581","authenticated-orcid":true,"given":"Daiki","family":"Taniyama","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-6233","authenticated-orcid":true,"given":"Michael","family":"Kruhlak","sequence":"additional","affiliation":[{"name":"CCR Microscopy Core, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-0758","authenticated-orcid":true,"given":"Yves","family":"Pommier","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Oberdoerffer","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-2081","authenticated-orcid":true,"given":"Travis H.","family":"Stracker","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2693-3234","authenticated-orcid":true,"given":"Urbain","family":"Weyemi","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb5414"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2024.195029"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15755"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00335-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00394-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3007"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05842"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2422029122"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422488112"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.02.026"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1695"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.101"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.24.10242"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01819"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102443"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115540"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.624"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.071"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202211267"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103503"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.04.029"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208821"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","unstructured":"A. Dhall D. Taniyama F. Elloumi A. Luna S. Varma S. Kumar L. Escobedo M. I. Aladjem C. E. Redon N. Roper W. C. Reinhold J. Del Rivero Y. Pommier Bimodal genomic approach predicting Semaphorin 7A (SEMA7A) as prognostic biomarker in adrenocortical carcinoma. bioRxiv 2025.04.03.647086 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.04.03.647086.","DOI":"10.1101\/2025.04.03.647086"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005674"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2018.01.022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.084"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10040627"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12321"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2548"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3393"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep18100"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47008-x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.52601\/bpr.2025.250008"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth866"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz518"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13981-x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008511"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113896"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37341-y"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3172"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1231"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.03.030"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03345"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf766"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aed4161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:32:41Z","timestamp":1790022761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aed4161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":46,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,9,11]]}},"alternative-id":["10.1126\/sciadv.aed4161"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aed4161","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2025-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaed4161"}}