Polynucleotide cross-linking by aluminum.
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.
Karlik
S J
SJ
Department of Diagnostic Radiology, University Hospital, University of Western Ontario, London, Canada.
Eichhorn
G L
GL
D000535:Aluminum; D000818:Animals; D001482:Base Composition; D002417:Cattle; D003016:Clostridium perfringens / Q000235:genetics; D003432:Cross-Linking Reagents; D004247:DNA; D004269:DNA, Bacterial; D006358:Hot Temperature; D008837:Micrococcus / Q000235:genetics; D009691:Nucleic Acid Denaturation; D011067:Poly dA-dT; D011089:Polydeoxyribonucleotides; D011119:Polynucleotides
D003432:Cross-Linking Reagents; D004269:DNA, Bacterial; D011089:Polydeoxyribonucleotides; D011119:Polynucleotides; D011067:Poly dA-dT; C019530:poly(dC-dG); D004247:DNA; D000535:Aluminum