Eukaryotic DNA Topoisomerase II is a ubiquitous ATP-dependent type II Topoisomerase that play an important role in DNA replication, transcrIPPtion and recombination by changing the degree of superhelicity, catenation and knotting of topologically closed DNA molecules. Two isoforms of DNA Topoisomerases II have been reported in mammalian cells, Topoisomerase II and II. cDNA sequence of those isoforms reveals that both type II Topoisomerases are structurally and catalytically close. However, Topoisomerase II is expressed with no cell cycle dependence, whereas the expression of Topoisomerase II is cell cycle-regulated, peaking in G2-M phase and declining to a minimal level at the end of M phase. Topoisomerase II is polyubiquitinated and degraded preferentially in apoptosis induced human epithermoid carcinoma-derived cell line, MA1 cell, in an ATP-and-ubiquitin-dependent manner. Recent studies also indicated that this isoform is selectively cleaved during Fas-mediated T cell apoptosis and Fas-, Staurosporine- and Anisomycin-mediated Jurkat cell apoptosis.