If you studied biology in high school, you may remember the chapter about DNA, also known as the chapter no one actually read. DNA structure and replication are some of the most complex elements of simple biology, and this week, scientists discovered that everything we thought about it is wrong, wrong, wrong.
Using cutting-edge technology called electron microscopy (EM), which uses an electron beam to create an image, kind of like an ultrasound uses sound waves to create pictures, a team of scientists has assembled the first-ever pictures of a complete replisome, the protein complex that enables DNA to copy itself. That picture turned out to be very different from what scientists and textbook writers had imagined.
"All the textbook drawings and descriptions of how a replisome should look and work are based on biochemical and genetic studies," said biologist and study coauthor Huilin Li, in a press release.
He said that previous attempts to picture the replisome have been like the famous parable of three blind men trying to describe an elephant. If you haven't heard that one, the three men crowd around the pachyderm and touch her various body parts — tusk, tail, foot — and then try to come to an agreement about what she actually looks like. Hilariously, they are all way off and, presumably, in the presence of one very displeased elephant.
Previous textbook drawings show the helicase (a binder that secures the DNA strands, like the end of a shoelace) moving along the DNA and splitting the two strands apart. The helicase is pictured with two polymerases (DNA creators) located at its back, where the DNA strand splits in two. However, the actual images show something quite different.
Only one polymerase is on the back of the helicase, while the other is on the front side, where the helices first touches noses with the double-helix. That means that one polymerase (the lazy one) gets to sit on the back side and zip loose ends up, while the other has to sit at the front, then run to the back to help Lazy Polymerase #2 with the clean-up, performing this lap over and over until replication is complete.
At first, the researchers were so taken aback by what they found that they asked colleagues from another institute to double-check their work. Indeed, the second group of scientists used different technology and came to the same conclusion. As yet, the scientists aren't sure why Polymerase #1 sits at the front, instead of keeping to the back with his lazy brother.
The excited scientists can't wait to see what they find next, in studying the function of the mysterious polymerase.
"DNA replication is one of the most fundamental processes of life," said Jingchuan Sun, an EM expert in Li's lab, "so it is every biochemist's dream to see what a replisome looks like."
Sun, Li, and their colleagues published the exciting images in the prestigious journal Nature.
