Figure 1.
Interaction of ataxin-3 and PNKP in normal and disease states.
‘Normal’ function of the ataxin-3–PNKP interaction is to coordinately promote DNA repair (top). However, in SCA3 ‘Disease’, polyglutamine-expanded ataxin-3 may sequester PNKP in aggregates to prevent PKNP-mediated DNA repair activity (lower left). Alternatively, in SCA3 ‘Disease’, polyglutamine-expanded ataxin-3 may prevent PKNP DNA repair function through an aggregate-independent mechanism by interacting with PKNP in its native complex to inhibit it (lower right).