First Evidence for Aluminum-maltol driven B to Z-DNA Conformational Transition in Poly d(GC). d(GC): Relevance to Alzheimer’s Disease

Order of Publishing in Issue: 
Volume :6
Issue :2
April, 2012
Page No: 
M. Govindaraju [1,4], Monica F.S.[2, 3], Berrocal R [3]., Sambasiva Rao K.R.S. [4] and Rao K.S. [3]*
[1] Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India
[2] Columbus University College of Medicine and Health Sciences, Republic Panama
[3] INDICASAT-AIP, City of Knowledge, Republic Panama
[4] Department of Biotechnology, Acharya Nagarjuna University, Guntur, India

Higher concentration of Aluminum (Al) has been observed in Alzheimer’s, Parkinson’s, and Amyotrophic lateral sclerosis and there was an apparent localization of the Al in chromatin in the brain cells. Studies of Al-DNA interaction showed that cross-linking occurs in DNAs of all base ratios, including poly d(AT).d(AT) and poly d(GC).d(GC). In the present investigation, interaction of Al with poly d(GC).d(GC) and poly d(AT).d(AT) was studied using Al-maltol, a hydrolytically stable Al-compound, at neutral pH. We found that Al at micromolar level caused conformational transition from B-DNA to Z-DNA in poly d(GC). d(GC). Chelation by EDTA could reverse the Z-DNA caused by Al-maltol back to B- DNA. We propose that Al(mal)2 + and Al(mal) 2+, major cationic species of Al-maltol at neutral pH are involved in the above transition in poly d(GC).d(GC). The biological relevance of DNA transition in Alzheimer’s disease is discussed.

Aluminum maltol, DNA transition, EDTA, Z DNA
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