DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (By similarity). Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Binds 1 magnesium or manganese ion per subunit. Can partially complement the absence of TDP1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity. Belongs to the CCR4/nocturin family. TTRAP/TDP2 subfamily.