DNA topoisomerase II and its growing repertoire of biological functions

Abstract

The importance of targeting toposimerase II (TOP2) for the treatment of cancer is not a new concept; however, understanding of the biological functions of this enzyme has lagged behind the use of the drugs to target it. This Review discusses what we now know about the functions of TOP2. DNA topoisomerases are enzymes that disentangle the topological problems that arise in double-stranded DNA. Many of these can be solved by the generation of either single or double strand breaks. However, where there is a clear requirement to alter DNA topology by introducing transient double strand breaks, only DNA topoisomerase II (TOP2) can carry out this reaction. Extensive biochemical and structural studies have provided detailed models of how TOP2 alters DNA structure, and recent molecular studies have greatly expanded knowledge of the biological contexts in which TOP2 functions, such as DNA replication, transcription and chromosome segregation — processes that are essential for preventing tumorigenesis.