Structural aspects of mammalian DNA replication: topoisomerase II.

The dynamic biology of mammalian DNA requires structural complexity. Previous studies on the structure and function of mammalian DNA have suggested that mammalian cell nuclei contain DNA organized into loop-domains by a nuclear structural subcomponent termed the nuclear matrix. The loop-domains, functioning as replicons during DNA synthesis, appear to be replicated by biosynthetic complexes located at fixed sites within the nuclear matrix milieu. Recently, we have found the mammalian DNA topoisomerase II enzyme to be associated with newly replicated DNA, and we speculate that the enzyme may be strategically positioned to untangle topologically intertwined daughter loop-domains before mitotic segregation. Further studies demonstrating growth-related elevations of DNA topoisomerase II levels in rat prostatic adenocarcinoma tissues support a role for the enzyme in cellular proliferation in vivo. The possible participation of DNA topoisomerase II in mammalian DNA replication and the proliferation-dependent appearance of the enzyme in neoplastic tissues may have important implications for therapeutic strategies directed at DNA topoisomerase II.