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TTRAP is a 5-prime tyrosyl-DNA phosphodiesterase that is required for efficient repair of topoisomerase II-induced DNA double-strand breaks. Thus it can remove lots of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, generating a free 5' phosphate to DNA. It also has 3'-tyrosyl DNA phophodiesterase activity, but not so efficient as TDP1. TTRAP functions as a negative regulator of ETS1 and inhibit nuclear factor-kappa-B activation.