topoisomerase and DNA gyrase
/ TOP-oh-eye-SOM-er-ase; JY-race /
Try to pull apart the two strands of a tightly twisted rope from the middle: the part of the rope ahead of your hands gets more and more overtwisted and kinked until you can hardly pull any further. DNA has exactly this problem during replication. As helicase unwinds the helix at the fork, the still-paired DNA ahead winds up tighter and tighter. Topoisomerases are the enzymes that relieve this twisting strain.
Topoisomerases work by transiently cutting the DNA backbone — either one strand (type I) or both strands (type II) — letting the DNA rotate or pass through the break to release the tension, and then sealing it back up perfectly. In bacteria, a type II enzyme called DNA gyrase goes a step further: it actively introduces negative supercoils, undertwisting the DNA, which both relieves the strain ahead of the fork and keeps the chromosome compact. Topoisomerases can also untangle two interlinked DNA circles (decatenation), which is essential to separate the two finished daughter chromosomes after a circular genome is copied.
Without topoisomerases the fork would grind to a halt within seconds as the supercoiling ahead became impossible to unwind. Because they are essential and because cutting DNA is dangerous if it goes wrong, topoisomerases are major drug targets: fluoroquinolone antibiotics jam bacterial gyrase, trapping it on broken DNA, and several anticancer drugs trap human topoisomerases on broken DNA to kill rapidly dividing cells.
Ciprofloxacin, a common antibiotic, works by jamming bacterial DNA gyrase mid-cut: the enzyme leaves the DNA broken and cannot reseal it, so the bacterium's chromosome falls apart and the cell dies — a direct medical payoff of understanding this enzyme.
Gyrase is essential — which makes it a prime antibiotic target.
Topoisomerases cut and reseal the sugar-phosphate backbone to change DNA topology; this is the opposite of helicase, which only breaks base-pair hydrogen bonds and never cuts the backbone.