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Fanconi anemia pathway regulates convergent transcription-induced cell death at trinucleo
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Nimrat Chatterjee, Yunfu Lin, and John H. Wilson
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Massachusetts Institute of Technology
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Department of Biology, MIT, Cambridge, MA 02139, USA
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nimratc@mit.edu
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Almost 20 incurable neurodegenerative disorders are caused by trinucleotide repeat (TNR) expansion beyond a certain threshold, with disease time of onset and severity positively correlating with repeat length. Typically, long TNRs display a bias toward further expansion and repeats continue to expand not only during germline transmissions from parents to offspring, but also remain highly unstable in somatic tissues of patients. Hence, understanding TNR instability mechanisms sheds light on underlying disease pathology. Recently, we showed that activated ATR (ataxia-telangiectasia mutated ï›ATMï and Rad3 related) is the major signal for convergent-transcription-induced cell death at CAG repeats and is regulated by the mismatch repair (MMR) pathway. Additionally, components of other DNA repair pathways such as transcription-coupled nucleotide excision repair (TC-NER) and R-loop resolution by RNaseH (ribonuclease H) reduce cell death. Because activated ATR signals ....
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