Polynucleotide cross-linking by aluminum

Abstract The observations that there was an increased concentration of Al in the brains of Alzheimer's, Guam-Parkinson, and amyotrophic lateral sclerosis disease patients and that there was an apparent localization of the Al in chromatin led to a study of the interaction of Al(III) with DNA. We have previously shown that Al cross-links calf thymus DNA at low pH (S. J. Karlik, G. L. Eichhorn, P. N. Lewis, and D. R. Crapper, Biochemistry 19, 5991 [1980]). Extended studies indicate that cross-linking occurs in DNAs of all base ratios, including polydAdT and polydGdC. Since Al cross-links prevent renaturation in polydAdT, the decrease in the amount of polymer renatured in the presence of Al becomes a quantitative appraisal of the extent of cross-linking. Saturation of cross-linking occurs at a 0.4 ratio of Al to nucleotide phosphate, indicating that potentially 80% of the base pairs are Al bound. Cross-links are broken at elevated pH and by EDTA.