Like zipper tabs, protein motors called "DNA helicases" unzip double-stranded DNA. This unzipping action prepares DNA for replication, recombination, and repair.

Frank Harmon. Stephen Kowalczykowski, and RJ DiGate, the latter from the University of Maryland, unexpectedly discovered that a DNA helicase, "RecQ," from the bacterium Escherichia coli (E. coli) can unwind covalently closed double-stranded DNA (a covalent bond is formed by shared electrons). A surprising finding given that helicases usually need a DNA end or a single-stranded region to initiate unwinding.

Experiments also revealed that the unwinding action of RecQ profoundly stimulates the E. coli enzyme Topoisomerase III (Topo III), the first evidence of a functional interaction between RecQ and Topo III.

As RecQ unwinds double-stranded DNA, Topo III recognizes an unidentified attribute of the RecQ-DNA complex and is attracted to binding sites on the single DNA strands.

Their research led the three scientists to propose a model in which, like needles pulling thread, Topo III attaches to and sequentially pulls each single DNA strand across a second DNA molecule. This "strand passage activity" results in two intertwined double-stranded DNA molecules, which look like links of a chain. The linked DNA molecules are deemed "catenated."

RecQ-Topo III interaction has implications for the maintenance of genetic stability because the unzipping function of RecQ also initiates genetic recombination and suppresses illegitimate recombination.

Past studies have suggested that the DNA strand passage activity of Topo III is a potential means of recombination control; since RecQ specifically stimulates Topo III, it may be that RecQ and Topo III work in concert to control and stabilize recombination in E. coli.

Harmon, Kowalczykowski, and DiGate believe their model may be what scientists will find in people because two different proteins similar to E. coli Topo III have been identified in humans. In addition, two human DNA helicases, Blm and Wrn, share similarities with RecQ.

Since mutations in Wrn and Blm result in diseases, Werner's and Bloom's syndromes respectively, characterized by cells with pronounced genomic instability, it's highly likely that the Wrn and Blm helicases are intimately involved in the orderly recombination and segregation of chromosomes. (People with the rare, inherited Werner's syndrome age prematurely; most victims die before reaching 50. Children with Bloom's syndrome have small bodies and are prone to cancer, chronic lung disease, and diabetes.)

If human helicases and topoisomerases interact to control recombination according to the RecQ-Topo III model, it's possible that the loss of their combined strand passage activity results in incorrect amounts and types of recombination.

Reference: Harmon FG, RJ DiGate, and SC Kowalczykowski. Molecular Cell 3:611-620.