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Polynucleotide cross-linking by aluminum
1Department of Diagnostic Radiology, University Hospital, University of Western Ontario, London, Canada.
Journal of Inorganic Biochemistry
|December 1, 1989
Summary
Aluminum (Al) cross-links DNA, potentially binding 80% of base pairs at saturation. This DNA cross-linking was observed across various DNA types and may relate to neurodegenerative diseases involving increased brain aluminum.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Elevated aluminum (Al) concentrations are observed in the brains of patients with Alzheimer's disease, Guam-Parkinson disease, and amyotrophic lateral sclerosis.
- Aluminum appears to localize within the chromatin of affected brain cells.
Purpose of the Study:
- To investigate the interaction of aluminum(III) with DNA.
- To understand the mechanism and extent of Al-induced DNA cross-linking.
Main Methods:
- Studied the cross-linking of calf thymus DNA and synthetic polynucleotides (polydAdT, polydGdC) with Al(III) at low pH.
- Quantified cross-linking by measuring the inhibition of DNA renaturation in polydAdT.
- Determined saturation point for Al binding to DNA.
Main Results:
- Aluminum (Al) cross-links DNA across all base ratios studied.
- Al-induced cross-links prevent DNA renaturation, providing a quantitative measure of cross-linking.
- Cross-linking saturates at an Al to nucleotide phosphate ratio of 0.4, suggesting potential binding to 80% of base pairs.
- These cross-links can be reversed by increasing pH or using EDTA.
Conclusions:
- Aluminum(III) effectively cross-links DNA, impacting its structural integrity.
- The extent of DNA cross-linking by aluminum is significant, potentially affecting 80% of base pairs at saturation.
- The findings suggest a potential molecular mechanism linking aluminum accumulation in the brain to neurodegenerative diseases.