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Model for the assembly and activation of DNA-PK in vivo. Ku binds to the double-stranded DNA end, translocates in an ATP-independent manner to uncover the DNA end, and stabilizes the binding of p460 to the DNA end. Cooperative interactions among Ku, p460, and the DNA lead to efficient activation of the kinase. Our data indicate that both Ku and p460 contact the DNA, but their relative positions at the DNA end remain undetermined.
