Molecular understanding of aluminum-induced topological changes in(\[CCG_12\]) triplet repeats: relevance to neurological disorders.

Latha, K. S. and Anitha, S. and Jagannatha Rao, K. S. and Viswamitra, M. A. (2002) Molecular understanding of aluminum-induced topological changes in(\[CCG_12\]) triplet repeats: relevance to neurological disorders. Biochimica et Biophysica Acta, 1588. pp. 56-64. ISSN 0925-4439

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Abstract

Recent studies have shown that gene mutations are involved in the pathology of neurological disorders. CCG repeats cause genetic instability and are localized at the 5Vend of the non-coding regions of the FMR1 gene in fragile X syndrome. Our studies for the first time showed that aluminum (Al) levels were elevated in the serum samples of fragile X syndrome and also provide evidence for the interaction of aluminum with (\[CCG_12\])-repeats. Circular dichroism spectroscopic studies of (\[CCG_12\])indicated B-DNA conformation and in the presence of Al (\[10^5\]M) CCG repeats attained Z-DNA conformation. Further spectroscopic studies, which included melting profiles, ethidium bromide binding patterns and interaction of Z-DNA specific polyclonal antibodies confirmed the Z-conformation in (CCG)12-repeats in the presence of Al (\[10^5\]M). It is interesting to mention that Al-induced Z-conformation is stable even after the total removal of Al from CCG by desferoximine, a chelating drug. This is the first report to proof the role of Al in modulating the DNA (CCG repeats) topology and this information provides a clue about the possible involvement of Al at a molecular level in neurological/neurodegenerative disorders.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Elsevier Ltd.
Uncontrolled Keywords:	CCG-triplet repeat; Z-DNA; Fragile X syndrome; Aluminum; DNA topology
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology 500 Natural Sciences and Mathematics > 07 Life Sciences > 02 Evolution & genetics
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	26 Jun 2007 07:11
Last Modified:	28 Jun 2016 08:08
URI:	http://ir.cftri.res.in/id/eprint/1266

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