Anomalies in dye-terminator DNA sequencing caused by a natural G-quadruplex

A G-rich DNA sequence from yeast that can form a non-canonical G-quadruplex structure was cloned into a plasmid vector and subjected to Sanger sequencing using dye-labeled dideoxynucleotides. Two different effects were observed. In one, presence of the G4 sequence on the template strand led to incorrect incorporation of an A residue at an internal position in the G4 sequence. In the other, the nascent strand caused attenuation of the readout coincident with synthesis of the G-rich DNA. The two effects are novel examples of disruption in DNA synthesis caused by a G4 sequence. These results provide a new example of a DNA structure that could influence genomic stability in human cells.