{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:17:18Z","timestamp":1773213438877,"version":"3.50.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T00:00:00Z","timestamp":1482537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T00:00:00Z","timestamp":1482537600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Exposure to genotoxins such as ethanol\u2010derived acetaldehyde leads to DNA damage and liver injury and promotes the development of cancer. We report here a major role for the transforming growth factor \u03b2\/mothers against decapentaplegic homolog 3 adaptor \u03b22\u2010Spectrin (\u03b22SP, gene <jats:italic toggle=\"yes\">Sptbn1<\/jats:italic>) in maintaining genomic stability following alcohol\u2010induced DNA damage. \u03b22SP supports DNA repair through \u03b22SP\u2010dependent activation of Fanconi anemia complementation group D2 (Fancd2), a core component of the Fanconi anemia complex. Loss of \u03b22SP leads to decreased Fancd2 levels and sensitizes \u03b22SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both aldehyde dehydrogenase 2 and Fancd2 and resemble human fetal alcohol syndrome. <jats:italic toggle=\"yes\">Sptbn1<\/jats:italic>\u2010deficient cells are hypersensitive to DNA crosslinking agents and have defective DNA double\u2010strand break repair that is rescued by ectopic Fancd2 expression. Moreover, <jats:italic toggle=\"yes\">Fancd2<\/jats:italic> transcription in response to DNA damage\/transforming growth factor \u03b2 stimulation is regulated by the \u03b22SP\/mothers against decapentaplegic homolog 3 complex. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Dysfunctional transforming growth factor \u03b2\/\u03b22SP signaling impacts the processing of genotoxic metabolites by altering the Fanconi anemia DNA repair pathway. (H<jats:sc>epatology<\/jats:sc> 2017;65:678\u2010693)<\/jats:p>","DOI":"10.1002\/hep.28927","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T14:59:33Z","timestamp":1478357973000},"page":"678-693","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Loss of the transforming growth factor\u2010\u03b2 effector \u03b22\u2010Spectrin promotes genomic instability"],"prefix":"10.1097","volume":"65","author":[{"given":"Jian","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Nutrition,University of Texas MD Anderson Cancer Center,Houston,TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Nutrition,University of Texas MD Anderson Cancer Center,Houston,TX"},{"name":"Thoracic Oncology Section, 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