ANU scientists crack DNA replication mystery

The research findings were published in the prestigious international journal Cell this morning.

In all cells, DNA is copied by a large molecular machine called the replisome. The replisome does two things: it pulls the two DNA strands apart, and then it makes copies of both of the strands at the same time. “You can think of the strand separation part like a snowplough. The replisome tracks along one of the DNA strands and pushes the other one off it,” Professor Dixon said.

In certain bacteria, a small protein called TUS binds to the last part of DNA to be copied in a way that stops the replisome when it faces in one direction, but not in the other. How it can work this way has been a long standing puzzle.

The ANU team finally solved the important question of how TUS stops the replisome in this directional manner. “When the replisome comes along from one direction, separation of the two DNA strands simply knocks the TUS off as you'd expect. But when it comes from the other direction, the strand separation near TUS leads to one of the DNA bases flipping over and inserting itself like a key in a lock in a perfectly shaped pocket on the surface of TUS. TUS is locked onto the DNA and this stops the replisome snowplough in its tracks.”

Professor Dixon said the discovery was important “not just because it solved a fundamental scientific question, but also because TUS was found to lock onto the DNA very strongly and in an entirely new way.”

“Strong interactions like this have great potential to be used in bio- and nano-technology in fabricating new devices that might for example, be used for early detection of diseases,” Professor Dixon said.

“This discovery illustrates once again how the quest for fundamental knowledge can result in unexpected technological progress.”