Abstract
Previously, we evidenced a B → Z helical change in Alzheimer’s brain genomic DNA, leading to a hypothesis that Alzheimer’s disease (AD) etiological factors such as aluminum (Al), amyloid β (Aβ) peptide, and Tau might play a role in modulating DNA topology. In the present study, we investigated the interaction of Al and Aβ with DNA. Our results show that Aβ(1–42) could induce a B → ψ (Psi) conformational change in pUC 18 supercoiled DNA (scDNA), Aβ(1–16) caused an altered B-form, whereas Al induced a complex B-C-A mixed conformation. Ethidium bromide binding and agarose gel electrophoresis studies revealed that Al uncoiled the DNA to a fully relaxed form, whereas Aβ(1–42) and Aβ(1–16) effected a partial uncoiling and also showed differential sensitivity toward chloroquine-induced topoisomer separation. Our findings show for the first time that Aβ and Al modulate both helicity and superhelicity in scDNA. A new hypothetical model explaining the potential toxicity of Aβ and Al in terms of their DNA binding properties leading to DNA conformational alteration is proposed.
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This paper is dedicated to the memory of the late Prof. M. A. Viswamitra, Indian Institute of Science, Bangalore, India. M. L. Hegde and S. Anitha have contributed equally to this paper.
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Hegde, M.L., Anitha, S., Latha, K.S. et al. First evidence for helical transitions in supercoiled DNA by amyloid β peptide (1–42) and aluminum. J Mol Neurosci 22, 19–31 (2004). https://doi.org/10.1385/JMN:22:1-2:19
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DOI: https://doi.org/10.1385/JMN:22:1-2:19