한빛사논문
- 조회2,741
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.
1 Department of Biology, University of Pennsylvania,
Philadelphila, PA 19104, USA.
2 Howard Hughes Medical Institute,
University of Pennsylvania, Philadelphila, PA 19104, USA.
* To whom correspondence should be addressed.
논문정보
- Research article
- 2007년 03월 (BRIC 등록일 )
- 국외 연구진
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