DNA topoisomerases in cancer chemotherapy: basic and applied aspects

These conserved nuclear enzymes catalyse a variety of interconversions of DNA which take place between topological isoforms of the molecule, through transient cleavage, strand passing and re-ligation. In this context the DNA topoisomerases have been generally considered as good candidates to play a role in the enzymatic repair processes going on in the cell after DNA damage inflicted by either physical or chemical agents. It has been suggested that this role could be direct, with the actual participation of topoisomerases in the molecular mechanism of lesion repair, as for example in the excision of base damage or DNA strand break repair. Alternatively, it could be indirectly responsible for the preparative steps in the relaxation of chromatin in order to allow repair enzymes to gain access to damaged DNA.