S1 nuclease sensitivity to cis- and trans-diamminedichloroplatinum(II) modified DNAs: Influence of (G+C) content and nucleotide sequence

Abstract

The sensitivity of S1 nuclease to cis- and trans-(NH 3) 2PtCl 2 modified DNAs is examined as a function of (1) the level of cis- and trans-(NH 3) 2PtCl 2 bound, (2) the % (G+C) content in DNA from different sources and (3) the sequence dependence in poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC). The extent of DNA digested increases with increasing levels of either isomer and is inversely influenced by the % (G+C) content of the DNA. However, the difference in the extent of digestion between the cis-and trans-(NH 3) 2PtCl 2 modified DNAs at equivalent levels of bound isomer follows the order, calf-thymus > M. lysodeikticus > poly(dG-dC).poly(dG-dC). While there is virtually no difference in the digestion profiles for poly(dG-dC).poly(dG-dC) modified with the two isomers, there is a striking difference in the extent of digestion between cis- and trans-(NH 3) 2PtCl 2 modified poly(dG).poly(dC). These results are discussed in light of (1) the possible modes of binding for cis-(NH 3) 2PtCl 2, (2) previously reported findings on modified DNA and (3) possible implications for modifications in cellular chromatin.