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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5820
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pubmed:dateCreated |
2007-3-30
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
30
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pubmed:volume |
315
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1857-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17332375-Alleles,
pubmed-meshheading:17332375-Animals,
pubmed-meshheading:17332375-Animals, Genetically Modified,
pubmed-meshheading:17332375-Anticipation, Genetic,
pubmed-meshheading:17332375-CREB-Binding Protein,
pubmed-meshheading:17332375-DNA Repair,
pubmed-meshheading:17332375-Drosophila Proteins,
pubmed-meshheading:17332375-Drosophila melanogaster,
pubmed-meshheading:17332375-Female,
pubmed-meshheading:17332375-Fragile X Syndrome,
pubmed-meshheading:17332375-Genomic Instability,
pubmed-meshheading:17332375-Histone Deacetylase Inhibitors,
pubmed-meshheading:17332375-Humans,
pubmed-meshheading:17332375-Huntington Disease,
pubmed-meshheading:17332375-Hydroxamic Acids,
pubmed-meshheading:17332375-Machado-Joseph Disease,
pubmed-meshheading:17332375-Male,
pubmed-meshheading:17332375-Models, Animal,
pubmed-meshheading:17332375-Peptides,
pubmed-meshheading:17332375-Transcription, Genetic,
pubmed-meshheading:17332375-Transgenes,
pubmed-meshheading:17332375-Trinucleotide Repeat Expansion,
pubmed-meshheading:17332375-Trinucleotide Repeats
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pubmed:year |
2007
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pubmed:articleTitle |
CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease.
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pubmed:affiliation |
Department of Biology, University of Pennsylvania, Philadelphila, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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