Extreme mechanical diversity of human telomeric DNA revealed by fluorescence-force spectroscopy

Significance G-quadruplex (GQ)–forming G4 DNA, made of four repeats of guanines, is implicated in many important processes. Telomeric GQs are being studied extensively as anticancer drug targets. Because many nucleic acid-processing enzymes can exert piconewton forces and can be functionally regulated by tension on DNA, we used a single-molecule instrument combining fluorescence with mechanical manipulation to study the dynamics of human telomeric DNA under physiological levels of tension. We observed extreme mechanical diversity with at least six different interconverting species that differ in mechanical responses. Such extreme mechanical diversity may induce differential interactions with helicases and polymerases and modulate processes such as replication and transcription. Our comparative analysis further revealed the effects of sequence changes and ionic conditions.