{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:00:34Z","timestamp":1777485634803,"version":"3.51.4"},"reference-count":146,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM110631"],"award-info":[{"award-number":["R15GM110631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Roberts syndrome (RBS) is a multispectrum developmental disorder characterized by severe limb, craniofacial, and organ abnormalities and often intellectual disabilities. The genetic basis of RBS is rooted in loss-of-function mutations in the essential N-acetyltransferase ESCO2 which is conserved from yeast (Eco1\/Ctf7) to humans. ESCO2\/Eco1 regulate many cellular processes that impact chromatin structure, chromosome transmission, gene expression, and repair of the genome. The etiology of RBS remains contentious with current models that include transcriptional dysregulation or mitotic failure. Here, we report evidence that supports an emerging model rooted in defective DNA damage responses. First, the results reveal that redox stress is elevated in both eco1 and cohesion factor Saccharomyces cerevisiae mutant cells. Second, we provide evidence that Eco1 and cohesion factors are required for the repair of oxidative DNA damage such that ECO1 and cohesin gene mutations result in reduced cell viability and hyperactivation of DNA damage checkpoints that occur in response to oxidative stress. Moreover, we show that mutation of ECO1 is solely sufficient to induce endogenous redox stress and sensitizes mutant cells to exogenous genotoxic challenges. Remarkably, antioxidant treatment desensitizes eco1 mutant cells to a range of DNA damaging agents, raising the possibility that modulating the cellular redox state may represent an important avenue of treatment for RBS and tumors that bear ESCO2 mutations.<\/jats:p>","DOI":"10.1093\/g3journal\/jkab426","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T12:10:31Z","timestamp":1639397431000},"source":"Crossref","is-referenced-by-count":9,"title":["Genetically induced redox stress occurs in a yeast model for Roberts syndrome"],"prefix":"10.1093","volume":"12","author":[{"given":"Michael G","family":"Mfarej","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4216-8306","authenticated-orcid":false,"given":"Robert V","family":"Skibbens","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Lehigh University , Bethlehem, PA 18015, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"2022072011080710900_jkab426-B1","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1101\/gad.8.20.2401","article-title":"The SAD1\/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast","volume":"8","author":"Allen","year":"1994","journal-title":"Genes Dev"},{"key":"2022072011080710900_jkab426-B2","doi-asserted-by":"crossref","first-page":"49542","DOI":"10.1074\/jbc.M404324200","article-title":"The spindle pole body assembly component Mps3p\/Nep98p functions in sister chromatid cohesion","volume":"279","author":"Antoniacci","year":"2004","journal-title":"J Biol 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