A model of DNA damage repair dysfunction in the HD pathology mediated by Ku70. Interaction between mutant Htt and Ku70 inhibits complex formation among Ku70, Ku80, and DNA–PKcs and represses the DSB repair activity of the DNA–PK complex. Ku70 bound to mutant Htt undergoes protein degradation by the proteasome system. Coaggregation to inclusion bodies also occurs, but functional impairment of the DNA–PK complex occurs more promptly by interaction before quantitative alteration of Ku70.