Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (By similarity). May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity). ATP-dependent breakage, passage and rejoining of double-stranded DNA. Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+). Homodimer (By similarity). Interacts with COPS5 (By similarity). Interacts with RECQL5; this stimulates DNA decatenation (By similarity). Interacts with SETMAR; stimulates the topoisomerase activity (By similarity). Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (By similarity). Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner (By similarity). Interacts with MCM3AP (By similarity). Interacts with ERCC6 (By similarity). Interacts with PLSCR1 (By similarity). Interacts with GCNA; this interaction allows the resolution of topoisomerase II (TOP2A) DNA-protein cross-links (By similarity). Phosphorylation has no effect on catalytic activity (By similarity). However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation (By similarity). Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils. Belongs to the type II topoisomerase family.