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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
31
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pubmed:dateCreated |
2006-8-2
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pubmed:databankReference |
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pubmed:abstractText |
The DNA abnormality found in 98% of Friedreich's ataxia (FRDA) patients is the unstable hyperexpansion of a GAA.TTC triplet repeat in the first intron of the frataxin gene. Expanded GAA.TTC repeats result in decreased transcription and reduced levels of frataxin protein in affected individuals. Beta-alanine-linked pyrrole-imidazole polyamides bind GAA.TTC tracts with high affinity and disrupt the intramolecular DNA.DNA-associated region of the sticky-DNA conformation formed by long GAA.TTC repeats. Fluorescent polyamide-Bodipy conjugates localize in the nucleus of a lymphoid cell line derived from a FRDA patient. The synthetic ligands increase transcription of the frataxin gene in cell culture, resulting in increased levels of frataxin protein. DNA microarray analyses indicate that a limited number of genes are significantly affected in FRDA cells. Polyamides may increase transcription by altering the DNA conformation of genes harboring long GAA.TTC repeats or by chromatin opening.
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pubmed:grant |
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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 |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11497-502
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16857735-Cell Line,
pubmed-meshheading:16857735-Friedreich Ataxia,
pubmed-meshheading:16857735-Humans,
pubmed-meshheading:16857735-Iron-Binding Proteins,
pubmed-meshheading:16857735-Ligands,
pubmed-meshheading:16857735-Molecular Structure,
pubmed-meshheading:16857735-Nucleic Acid Conformation,
pubmed-meshheading:16857735-Nylons,
pubmed-meshheading:16857735-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:16857735-Transcription, Genetic,
pubmed-meshheading:16857735-Trinucleotide Repeats
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pubmed:year |
2006
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pubmed:articleTitle |
DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA.TTC repeats in Friedreich's ataxia.
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pubmed:affiliation |
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, 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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