It’s tricky to make an exact copy of yourself. Or at least it is for cells undergoing mitosis, where cells replicate everything inside of them, including their neatly packaged DNA, then split in half. Rice University professor Peter Wolynes is interested in how the packaged DNA, called a chromosome, changes its structure during replication, going from a ball shape to a cylinder shape that can be transported easily to the daughter cell. He recently published a paper in PNAS describing how this could rely on a specific type of two-motor system.
“When a cell undergoes mitosis, its chromosomes break symmetry,” Wolynes said. “They go from a ball shape, which is symmetrical in every direction, to a cylinder shape that loses the spherical symmetry a ball has.”
When the chromosomes are in the ball shape during most of the cell’s life, they have little loops sticking out of them, like a ball of yarn that a cat has lightly played with. In an earlier Nature Communications paper, Wolynes’ team described how a two-motor system that tugged on those loops can eventually pull the ball into a cylinder shape.
“We know the key proteins act as motors consuming energy,” Wolynes explained. “In our first paper, we proposed a system in which these motor proteins could pull on the extruded loops of the DNA, eventually causing the balls to deform into a cylinder.”
Wolynes’s team revisited the theory, this time thinking about the way the two different motors acted differently from each other. One type of motor, a processive one, binds to a loop of DNA and continuously pulls, staying for quite a while in one spot. A nonprocessive motor binds to a loop of DNA and only pulls a little, but before it can pull again, it would usually fall off and start over. When the researchers ran their models with the first motor working as a nonprocessive motor and the second as a processive motor, they found that their simulations closely matched the data.
“Our model shows that the processivity of the motor helps break the symmetry,” said Zhiyu Cao, a postdoctoral fellow and first author on the paper. “The symmetry breaking occurring locally is what drives the deformation of the ball into the observed cylinder globally.”
Imagine the cat playing with the yarn ball. The cat’s front claws, the processive motors, get stuck in the yarn, and they pull and pull and pull at the same spots. Meanwhile, their back claws, the nonprocessive motors, remain unstuck, so the cat uses those to pull at different places in the yarn ball as they play. Eventually, the pulling will change the shape of the yarn ball, breaking its symmetry.
The processive model leads to a strange feature in the chromosome structure if the chromosome is not uniform in its ability to bind the motor. If a loop is near the intersection where an active region of DNA borders an inactive region, the active region ends up more likely to have a processive motor on it, leading to an observed structural pattern called a “chromosomal jet” that was previously unexplained.
In the model where both motors were nonprocessive, the chromosome cylinder eventually turns out to be a crystal but a rather soft one: The subunits were periodically organized, but not as tightly as they are in more commonly known hard crystals. In the model with both processive and nonprocessive motors, the resulting cylinder is not fully crystalline but takes on a smectic liquid crystalline structure, similar to the slippery soap film that appears when you wash your hands. This structure’s organization is looser and layered, giving it much more flexibility and perhaps the ability to be moved.
“The structure of the cylinder is related to its broken symmetry,” Wolynes said. “This study raises the question, why do eukaryotic chromosomes, like those of humans, undergo broken symmetry changes, but apparently bacterial chromosomes do not need to do so?”
The theoretical notion of broken symmetry is important throughout physics and even in cosmology, Wolynes added. Finding the mechanisms of broken symmetry in chromosomal biophysics should inspire new experiments and lead to a deeper understanding of how a cell copies itself.
This work was funded by the Bullard-Welch Chair at Rice (C-0016) and the National Science Foundation (PHY- 2019745.)