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We employed functional protein arrays to identify molecular changes induced in a human bronchial epithelial cell line (HBEC3-KT) and osteosarcoma cell line (U2OS) and evaluated their impact on outcomes associated with radiation induced genomic instability (RIGI) at day 5 and 7 post-exposure to a 2Gy X-ray dose, which revealed replication stress in the context of increased FOXM1b expression. Irradiated cells had reduced DNA replication rate detected by the DNA fiber assay and increased DNA resection detected by RPA foci and phosphorylation. Irradiated cells increased utilization of homologous recombination-dependent repair detected by a gene conversion assay and DNA damage at mitosis reflected by RPA positive chromosomal bridges, micronuclei formation and 53BP1 positive bodies in G1, all known outcomes of replication stress. Interference with the function of FOXM1, a transcription factor widely expressed in cancer, employing an aptamer, decreased radiation-induced micronuclei formation and cell transformation while plasmid-driven overexpression of FOXM1b was sufficient to induce replication stress, micronuclei formation and cell transformation.<\/jats:p>","DOI":"10.1371\/journal.pone.0235998","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T13:42:10Z","timestamp":1606743730000},"page":"e0235998","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Replication stress and FOXM1 drive radiation induced genomic instability and cell transformation"],"prefix":"10.1371","volume":"15","author":[{"given":"Zhentian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Doetsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8183-1601","authenticated-orcid":true,"given":"Erica","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"issue":"2","key":"pone.0235998.ref001","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.clon.2014.10.005","article-title":"Evidence-based estimates of the demand for radiotherapy","volume":"27","author":"GP Delaney","year":"2015","journal-title":"Clin Oncol (R Coll Radiol)"},{"issue":"1","key":"pone.0235998.ref002","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1667\/RR0527.1","article-title":"Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects","volume":"167","author":"H Suit","year":"2007","journal-title":"Radiat Res"},{"issue":"4","key":"pone.0235998.ref003","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1470-2045(11)70061-4","article-title":"Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries","volume":"12","author":"A Berrington de Gonzalez","year":"2011","journal-title":"Lancet Oncol"},{"key":"pone.0235998.ref004","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fonc.2013.00073","article-title":"Radiotherapy-induced malignancies: review of clinical features, pathobiology, and evolving approaches for mitigating risk","volume":"3","author":"S Braunstein","year":"2013","journal-title":"Frontiers in oncology"},{"issue":"11","key":"pone.0235998.ref005","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.celrep.2015.08.015","article-title":"Mutational Analysis of Ionizing Radiation Induced Neoplasms","volume":"12","author":"AL Sherborne","year":"2015","journal-title":"Cell Rep"},{"issue":"13","key":"pone.0235998.ref006","article-title":"Mutational landscape in genetically engineered, carcinogen-induced, and radiation-induced mouse sarcoma","volume":"4","author":"CL Lee","year":"2019","journal-title":"JCI Insight"},{"issue":"3","key":"pone.0235998.ref007","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/carcin\/21.3.397","article-title":"Radiation carcinogenesis","volume":"21","author":"JB Little","year":"2000","journal-title":"Carcinogenesis"},{"issue":"5","key":"pone.0235998.ref008","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1080\/09553002.2018.1564083","article-title":"A historical reflection on our understanding of radiation-induced DNA double strand break repair in somatic mammalian cells; interfacing the past with the present","volume":"95","author":"AA-O Shibata","year":"2019","journal-title":"International Journal of Radiation Biology"},{"issue":"7267","key":"pone.0235998.ref009","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"SP Jackson","year":"2009","journal-title":"Nature"},{"issue":"5","key":"pone.0235998.ref010","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1667\/0033-7587(2003)159[0581:NADEOE]2.0.CO;2","article-title":"Non-targeted and delayed effects of exposure to ionizing radiation: II. 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Sato","year":"2013","journal-title":"Mol Cancer Res"},{"issue":"1","key":"pone.0235998.ref026","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/00004032-200307000-00011","article-title":"Cancer risks from medical radiation","volume":"85","author":"E Ron","year":"2003","journal-title":"Health Phys"},{"issue":"12","key":"pone.0235998.ref027","doi-asserted-by":"crossref","first-page":"4744","DOI":"10.3390\/ijerph9124744","article-title":"Second malignant neoplasms following radiotherapy","volume":"9","author":"S Kumar","year":"2012","journal-title":"Int J Environ Res Public Health"},{"issue":"10","key":"pone.0235998.ref028","doi-asserted-by":"crossref","first-page":"e108234","DOI":"10.1371\/journal.pone.0108234","article-title":"Opposite roles for p38MAPK-driven responses and reactive oxygen species in the persistence and resolution of radiation-induced genomic instability","volume":"9","author":"E Werner","year":"2014","journal-title":"PLoS 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Adamson","year":"2012","journal-title":"Nat Cell Biol"},{"issue":"5","key":"pone.0235998.ref043","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/nprot.2007.77","article-title":"Cytokinesis-block micronucleus cytome assay","volume":"2","author":"M Fenech","year":"2007","journal-title":"Nat Protoc"},{"issue":"3","key":"pone.0235998.ref044","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/ncb2201","article-title":"53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress","volume":"13","author":"C Lukas","year":"2011","journal-title":"Nat Cell Biol"},{"issue":"12","key":"pone.0235998.ref045","doi-asserted-by":"crossref","DOI":"10.3390\/genes9120623","article-title":"The Unresolved Problem of DNA Bridging","volume":"9","author":"M Fernandez-Casanas","year":"2018","journal-title":"Genes 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Monteiro","year":"2013","journal-title":"Oncogene"},{"issue":"32","key":"pone.0235998.ref049","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1038\/onc.2013.457","article-title":"FOXM1 targets NBS1 to regulate DNA damage-induced senescence and epirubicin resistance","volume":"33","author":"P Khongkow","year":"2014","journal-title":"Oncogene"},{"issue":"2","key":"pone.0235998.ref050","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1389450115666141122211549","article-title":"Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance","volume":"17","author":"G Nestal de Moraes","year":"2016","journal-title":"Curr Drug Targets"},{"issue":"23","key":"pone.0235998.ref051","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1016\/j.jmb.2013.03.040","article-title":"Replication dynamics: biases and robustness of DNA fiber analysis","volume":"425","author":"H Techer","year":"2013","journal-title":"J Mol 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Burrell","year":"2013","journal-title":"Nature"},{"issue":"21","key":"pone.0235998.ref055","doi-asserted-by":"crossref","first-page":"5961","DOI":"10.1158\/1078-0432.CCR-12-0039","article-title":"FoxM1 inhibition sensitizes resistant glioblastoma cells to temozolomide by downregulating the expression of DNA-repair gene Rad51","volume":"18","author":"N Zhang","year":"2012","journal-title":"Clin Cancer Res"},{"issue":"5","key":"pone.0235998.ref056","doi-asserted-by":"crossref","first-page":"e96989","DOI":"10.1371\/journal.pone.0096989","article-title":"FOXM1 modulates cisplatin sensitivity by regulating EXO1 in ovarian cancer","volume":"9","author":"J Zhou","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"pone.0235998.ref057","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/ncb1217","article-title":"FoxM1 is required for execution of the mitotic programme and chromosome stability","volume":"7","author":"J Laoukili","year":"2005","journal-title":"Nat Cell 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malignant phenotype on human bronchial epithelial cells","volume":"66","author":"M Sato","year":"2006","journal-title":"Cancer Res"},{"issue":"5","key":"pone.0235998.ref064","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrc3916","article-title":"Replication stress and cancer","volume":"15","author":"H Gaillard","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"pone.0235998.ref065","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.dnarep.2018.08.017","article-title":"Preserving replication fork integrity and competence via the homologous recombination pathway","volume":"71","author":"A Ait Saada","year":"2018","journal-title":"DNA Repair (Amst)"},{"issue":"3","key":"pone.0235998.ref066","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3390\/genes11030326","article-title":"Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites","volume":"11","author":"K Maccaroni","year":"2020","journal-title":"Genes 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Biol"},{"issue":"40","key":"pone.0235998.ref085","doi-asserted-by":"crossref","first-page":"6266","DOI":"10.1038\/sj.onc.1206640","article-title":"Sustained hepatic expression of FoxM1B in transgenic mice has minimal effects on hepatocellular carcinoma development but increases cell proliferation rates in preneoplastic and early neoplastic lesions","volume":"22","author":"OA Kalinina","year":"2003","journal-title":"Oncogene"},{"issue":"3","key":"pone.0235998.ref086","doi-asserted-by":"crossref","first-page":"396","DOI":"10.4161\/cc.10.3.14709","article-title":"Multiple faces of FoxM1 transcription factor: lessons from transgenic mouse models","volume":"10","author":"TV Kalin","year":"2011","journal-title":"Cell Cycle"},{"issue":"12","key":"pone.0235998.ref087","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1158\/0008-5472.CAN-10-4087","article-title":"FoxM1 in tumorigenicity of the neuroblastoma cells and renewal of the neural progenitors","volume":"71","author":"Z Wang","year":"2011","journal-title":"Cancer Res"},{"issue":"4","key":"pone.0235998.ref088","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/leu.2015.334","article-title":"FOXM1 is a therapeutic target for high-risk multiple myeloma","volume":"30","author":"C Gu","year":"2016","journal-title":"Leukemia"},{"issue":"7035","key":"pone.0235998.ref089","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature03482","article-title":"DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis","volume":"434","author":"J Bartkova","year":"2005","journal-title":"Nature"},{"issue":"7035","key":"pone.0235998.ref090","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nature03485","article-title":"Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions","volume":"434","author":"VG 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