Pataskar, Shashank S and Dash, Debasis and Brahmachari, Samir K (2001) Progressive Myoclonus Epilepsy [EPM1] repeat $d(CCCCGCCCCGCG)_n$ forms folded hairpin structures at physiological pH. In: Journal of Biomolecular Structure & Dynamics, 19 (2). pp. 293-306.
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Abstract
The secondary structure of DNA has been shown to be an important component in the mechanism of expansion of the trinucleotide repeats that are associated with many neurodegenerative disorders. Recently, expansion of a dodecamer repeat, (CCCCGCCCCGCG)n upstream of cystatin B acne has been shown to be the most common mutation associated with Progressive Myoclonus Epilepsy (EPM1) of Unverricht-Lundborg type. We have investigated structure of oligonucleotides containing one, two and three copies of the EPM1 repeat sequences at physiological pH. CD spectra and anomalous faster gel electrophoretic mobilty indicates formation of intramolecularly folded structures that are formed independent of concentration. Hydroxylamine probing allowed us to identify the C residues that are involved in C.G base pairing. Pl nuclease studies elucidated the presence of unpaired regions in the folded back structures. UV melting studies show biphasic melting curves for the oligonucleotides containing two and three EPM1 repeats. Our data suggests multiple hairpin structures for two and three repeat containing oligonucleotides. In this paper we show that oligonucleotides containing EPM1 repeat adopt secondary structures that may facilitate strand slippage thereby causing the expansion.
Item Type: | Journal Article |
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Publication: | Journal of Biomolecular Structure & Dynamics |
Publisher: | Academic Press |
Additional Information: | Copyright of this article belongs to Academic Press. |
Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
Date Deposited: | 17 Oct 2008 04:53 |
Last Modified: | 19 Sep 2010 04:50 |
URI: | http://eprints.iisc.ac.in/id/eprint/16028 |
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