CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease
- PMID: 17332375
- DOI: 10.1126/science.1139517
CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease
Abstract
Although expansion of trinucleotide repeats accounts for over 30 human diseases, mechanisms of repeat instability remain poorly understood. We show that a Drosophila model for the CAG/polyglutamine (polyQ) disease spinocerebellar ataxia type 3 recapitulates key features of human CAG-repeat instability, including large repeat changes and strong expansion bias. Instability is dramatically enhanced by transcription and modulated by nuclear excision repair and a regulator of DNA repair adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB)-binding protein-a histone acetyltransferase (HAT) whose decreased activity contributes to polyQ disease. Pharmacological treatment to normalize acetylation suppressed instability. Thus, toxic consequences of pathogenic polyQ protein may include enhancing repeat instability.
Comment in
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Medicine. Anticipating trouble from gene transcription.Science. 2007 Mar 30;315(5820):1800-1. doi: 10.1126/science.1141279. Science. 2007. PMID: 17395816 No abstract available.
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