Abstract
Tau is mainly distributed in cytoplasm and also found to be localized in the nucleus. There is limited data on DNA binding potential of Tau. We provide novel evidence on nicking of DNA by Tau. Tau nicks the supercoiled DNA leading to open circular and linear forms. The metal ion magnesium (a co-factor for endonuclease) enhanced the Tau DNA nicking ability, while an endonuclease specific inhibitor, aurinetricarboxylic acid (ATA) inhibited the Tau DNA nicking ability. Further, we also evidenced that Tau induces B-C-A mixed conformational transition in DNA and also changes DNA stability. Tau-scDNA complex is more sensitive to DNAse I digestion indicating stability changes in DNA caused by Tau. These findings indicate that Tau alters DNA helicity and integrity and also nicks the DNA. The relevance of these novel intriguing findings regarding the role Tau in neuronal dysfunction is discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Nucleus / genetics
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Cell Nucleus / metabolism*
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Cell Nucleus / pathology
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DNA Breaks, Single-Stranded / drug effects
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DNA Damage / drug effects
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DNA Damage / genetics
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DNA, Superhelical / chemistry
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DNA, Superhelical / genetics
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DNA, Superhelical / metabolism*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Humans
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Microscopy, Electron, Transmission
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Neurodegenerative Diseases / genetics*
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Neurodegenerative Diseases / metabolism*
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Neurodegenerative Diseases / pathology
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Nucleic Acid Conformation
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Phosphorylation
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / ultrastructure
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Tauopathies / genetics
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Tauopathies / metabolism
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Tauopathies / pathology
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tau Proteins / genetics
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tau Proteins / metabolism*
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tau Proteins / ultrastructure
Substances
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DNA, Superhelical
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DNA-Binding Proteins
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Recombinant Proteins
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tau Proteins