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Or should it be Hot off the Month? Nah. Either way, the topoisomerases are making a big splash this month. First, David Goodsell (who has been doing Molecules of the Month over at the PDB for 7 years now!) chose to highlight them for the month of January:
Each of your cells contains about 2 meters of DNA, all folded into the tiny space inside the nucleus, which is a million times smaller. As you might imagine, these long, thin strands can get tangled very easily in the busy environment of the nucleus. To make things even more complicated, DNA is a double helix, which must be unwound to access the genetic information. If you have ever tried to unravel the individual fibers in a piece of rope, you will understand the knotty problems that this can cause. To help with these problems, your cells build several different topoisomerase enzymes that untangle and relax DNA strands.
Check out the rest of the entry here!
Second, a new article in this week’s Nature shows how DNA gyrase, a type II topoisomerase, goes about its business. In Mechanochemical analysis of DNA gyrase using rotor bead tracking (subscription required for the entire article), magnetic tweezers were used to study the enzymatic activity of DNA gyrase on individual pieces of DNA containing a so-called ‘rotor bead’. This rotor bead was visible upon rotation of the DNA by the topoisomerases activity, and by carefully controlling tension in the DNA and ATP concentrations, the enzyme’s energy source, a model for DNA gyrase’s mechanochemistry was proposed. They observed bursts of rotation corresponding to processive steps of DNA gyrase along the DNA, which introduced negative supercoils in multiples of two, and that changes in DNA tension had no detectable effect on supercoiling velocity, though marked changes in processivity are observed. Their model proposes that processivity depends on the kinetic competition between dissociation from the DNA template and tension-sensitive DNA wrapping. Cool!
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Tres tres cool. In fact it’s so cool you have to wonder if the paper is any good. Thankfully, I don’t have to worry about such stuff anymore.
Jeff Gore gave a talk on this work this past September while visiting Vancouver, so while I can’t yet admit to having read the paper in full, I do know that its good science.
The rotor bead in particular is a really clever way to observe rotations in the DNA, though I’m not yet sure how widespread it’s use will be in other single-molecule experiments.