Oxidative Probing of the G4 DNA Structure by ZnP1 Porphyrin within Sequences of <i>MYC</i> and <i>TERT</i> Promotors

Abstract

The formation of G4 structures in a DNA double helix competes with the complementary strand, which can change the equilibrium G4 structures studied on single-strand models by classical structural methods. A relevant task is to develop methods for detecting and localizing G4 in extended double-stranded (ds) DNA in the promoter regions of the genome. The porphyrin derivative ZnP1 selectively binds and leads to photo-induced oxidation of guanine in G4 structures on single-stranded (ss) and dsDNA model systems. In this research, we show the oxidative effect of ZnP1 on native sequences of MYC and TERT oncogene promoters that potentially capable to form G4 structures. Single strand breaks in the guanine rich sequence caused by ZnP1 oxidation and subsequent cleavage of the DNA strand by Fpg glycosylase were identified and assigned to the nucleotide sequence. The detected break sites corresponded to sequences potentially capable of forming G4 structures. New data were obtained on the possibility of folding G4 structures in the presence of a complementary strand in the context of the DNA double helix of the natural sequence.