| Literature DB >> 28114741 |
Jian Chen1, Vivek Shukla1,2, Patrizia Farci3, Jaclyn Andricovich4, Wilma Jogunoori5, Lawrence N Kwong6, Lior H Katz1,7, Kirti Shetty8, Asif Rashid9, Xiaoping Su10, Jon White5, Lei Li11, Alan Yaoqi Wang12, Boris Blechacz1, Gottumukkala S Raju1, Marta Davila1, Bao-Ngoc Nguyen13, John R Stroehlein1, Junjie Chen11, Sang Soo Kim14, Heather Levin13, Keigo Machida15,16, Hidekazu Tsukamoto15,17,18, Peter Michaely19, Alexandros Tzatsos4, Bibhuti Mishra5,13,20, Richard Amdur13,20, Lopa Mishra5,13,20.
Abstract
Exposure to genotoxins such as ethanol-derived 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 β/mothers against decapentaplegic homolog 3 adaptor β2-Spectrin (β2SP, gene Sptbn1) in maintaining genomic stability following alcohol-induced DNA damage. β2SP supports DNA repair through β2SP-dependent activation of Fanconi anemia complementation group D2 (Fancd2), a core component of the Fanconi anemia complex. Loss of β2SP leads to decreased Fancd2 levels and sensitizes β2SP 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. Sptbn1-deficient cells are hypersensitive to DNA crosslinking agents and have defective DNA double-strand break repair that is rescued by ectopic Fancd2 expression. Moreover, Fancd2 transcription in response to DNA damage/transforming growth factor β stimulation is regulated by the β2SP/mothers against decapentaplegic homolog 3 complex.Entities:
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Year: 2016 PMID： 28114741 PMCID： PMC5432427 DOI： 10.1002/hep.28927
Source DB: PubMed Journal: Hepatology ISSN： 0270-9139 Impact factor: 17.425