New evidences on Tau-DNA interactions and relevance to neurodegeneration.
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.
Padmaraju
Vasudevaraju
V
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, CSIR Unit, Mysore 570020, India.
Indi
Shantinath Satappa
SS
Rao
Kosagi Sharaf Jagannatha
KS
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004278:DNA, Superhelical / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D016875:tau Proteins