title: Molecular understanding of aluminum-induced topological changes in (CCG)12 triplet repeats: relevance to neurological disorders.
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 5' end 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.
authors.affiliation: Centre for Human Genetics, Institute of Biotechnology, G-05, Discoverer, ITPL, Whitefield Road, Bangalore, India.
authors.forename: Kallur Siddaramaiah
authors.initials: KS
authors.lastname: Latha
authors.forename: Suram
authors.initials: S
authors.lastname: Anitha
authors.forename: Kosagi Sharaf Jagannatha
authors.initials: KS
authors.lastname: Rao
authors.forename: Mysore Ananthamurthy
authors.initials: MA
authors.lastname: Viswamitra
mesh_terms: D000535:Aluminum / Q000097:blood; D020137:Base Pair Mismatch; D002942:Circular Dichroism; D004247:DNA / Q000032:analysis / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004996:Ethidium / Q000737:chemistry; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000097:blood / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009942:Organometallic Compounds; D011753:Pyrones; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D013696:Temperature; D018911:Trinucleotide Repeats / Q000187:drug effects*
chemical_list: D000535:Aluminum; D004247:DNA; D004996:Ethidium; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; D011753:Pyrones; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C067527:aluminum maltolate