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Structure-Specific Recognition of Friedreich’s Ataxia (GAA)n Repeats by Benzoquinoquinoxaline Derivatives
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- Bergquist, Helen, 1979- (author)
- Stockholms universitet,Institutionen för molekylärbiologi och funktionsgenomik
- Nikravesh, Abbas (author)
- Fernández, Raquel Domingo (author)
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- Nguyen, Chi-Hung (author)
- Good, Liam (author)
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- (creator_code:org_t)
- Wiley, 2009
- 2009
- English.
- In: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 10:16, s. 2629-2637
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Expansion of GAA triplet repeats in intron 1 of the FXN gene reduces frataxin expression and causes Friedreich's ataxia. (GAA)nrepeats form non-B-DNA structures, including triple helix H-DNA and higher-order structures (sticky DNA). In the proposed mechanisms of frataxin gene silencing, central unanswered questions involve the characterization of non-B-DNA structure(s) that are strongly suggested to play a role in frataxin expression. Here we examined (GAA)nbinding by triplex-stabilizing benzoquinoquinoxaline (BQQ) and the corresponding triplex-DNA-cleaving BQQ-1,10-phenanthroline (BQQ-OP) compounds. We also examined the ability of these compounds to act as structural probes for H-DNA formation within higher-order structures at pathological frataxin sequences in plasmids. DNA-complex-formation analyses with a gel-mobility-shift assay and sequence-specific probing of H-DNA-forming (GAA)nsequences by single-strand oligonucleotides and triplex-directed cleavage demonstrated that a parallel pyrimidine (rather than purine) triplex is the more stable motif formed at (GAA)nrepeats under physiologically relevant conditions.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- DNA cleavage
- DNA
- frataxin
- gene expression
- triplet repeat
- Molecular biology
- Molekylärbiologi
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- ref (subject category)
- art (subject category)
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- NATURAL SCIENCES
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- Stockholm University
- Karolinska Institutet
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