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Significance We found that TGGAA DNA repeats, which are involved in the neurological disease spinocerebellar ataxia 31, are capable of assuming two different hairpin structures depending on repeat number parity. We determined the interconversion kinetics by single-molecule spectroscopy and probed the interconversion mechanism through elucidation of the TGGAA repeat stem structure. Our results suggest that the two hairpin structures interconvert through motion slippage, and the process can be explained by the overall stem stability and local destabilization of the kinked GGA motif. Divalent cations and stem length affected the equilibrium and kinetics of slippage. Our findings suggest a mechanism by which a binary dynamic property of DNA repeats may affect repeat expansion and may be applicable to other repetitive DNA systems.

Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion