An Extraordinarily Stable DNA Minidumbbell

The minidumbbell (MDB) is a new type of native DNA structure. At neutral pH, two TTTA or CCTG repeats can fold into the highly compact MDB with a melting temperature of ∼22 °C. Owing to the relatively low thermodynamic stability, MDBs have been proposed to be the structural intermediates that lead to efficient DNA repair escape and thus repeat expansions. In this study, we reveal that two CCTG repeats can also form an extraordinarily stable MDB with a melting temperature of ∼46 °C at pH 5.0. This unusual stability predominantly results from the formation of a three hydrogen bond C+·C mispair between the two minor groove cytosine residues. Due to the drastic stability change, the CCTG MDB, when combined with its complementary sequence, shows instant and complete structural conversions when the pH switches between 5.0 and 7.0, making the system serve as a simple and efficient pH-controlled molecular switch.