Does topoisomerase II specifically recognize and cleave hairpins, cruciforms and crossovers of DNA?

DNA topoisomerase II is an enzyme that specializes in DNA disentanglement. It catalyzes the interconversion of DNA between different topological states. This event requires the passage of one duplex through another one via a transient double-strand break. Topoisomerase II is able to process any type of DNA, including structures such as DNA juxtapositions (crossovers), DNA hairpins or cruciforms, which are recognized with high specificity. In this review, we focused our attention on topoisomerase II recognizing DNA substrates that possess particular geometries. A strong cleavage site, as we identified in pBR322 DNA in the presence of ellipticine (site 22), appears to be characterized by a cruciform structure formed from two stable hairpins. The same sequence could also constitute a four-way junction structure stabilized by interactions involving ATC sequences. The latter have been shown to be able to promote Holliday junctions. We reviewed the recent literature that deals with the preferential recognition of crossovers by various topoisomerases. The single molecule relaxation experiments have demonstrated the differential abilities of the topoisomerases to recognize crossovers. It appears that enzymes, which distinguish the chirality of the crossovers, possess specialized domains dedicated to this function. We also stress that the formation of crossovers is dependent on the presence of adequate stabilizing sequences. Investigation of the impact of such structures on enzyme activity is important in order to both improve our knowledge of the mechanism of action of the topoisomerase II and to develop new inhibitors of this enzyme.