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  Indian J Med Microbiol
 

Figure 3: Our hypothesis on the potential implications of sequence specific binding of α-Synuclein/Tau in neuronal cell death. Both α-Synuclein/Tau may bind to CG rich regions in the promoters of various genes and alter the conformation from B-DNA to altered B-DNA. The altered conformation in the promoter region could alter the binding of transcription factors and alter gene expression. The altered regulation of the gene expression may result in neuronal cell dysfunction and finally lead to neuronal cell death. The negative supercoils generated during transcription may induce the formation of Z-DNA in CG rich regions. Normally, after transcription the negative supercoils are relaxed and the Z-DNA is again converted to B-DNA. Both α-Synuclein/Tau may bind to Z-DNA conformation formed due to transcriptional stress and stabilize the Z-DNA conformation. Z-DNA stabilization may result in the inhibition of transcription factors binding or may stop the movement of RNA polymerase. This may lead to the suppression of genes and finally to neuronal cell dysfunction

Figure 3: Our hypothesis on the potential implications of sequence specific binding of α-Synuclein/Tau in neuronal cell death. Both α-Synuclein/Tau may bind to CG rich regions in the promoters of various genes and alter the conformation from B-DNA to altered B-DNA. The altered conformation in the promoter region could alter the binding of transcription factors and alter gene expression. The altered regulation of the gene expression may result in neuronal cell dysfunction and finally lead to neuronal cell death. The negative supercoils generated during transcription may induce the formation of Z-DNA in CG rich regions. Normally, after transcription the negative supercoils are relaxed and the Z-DNA is again converted to B-DNA. Both α-Synuclein/Tau may bind to Z-DNA conformation formed due to transcriptional stress and stabilize the Z-DNA conformation. Z-DNA stabilization may result in the inhibition of transcription factors binding or may stop the movement of RNA polymerase. This may lead to the suppression of genes and finally to neuronal cell dysfunction