New Model Reveals How Chromosomes Get Packed Up

October 7, 2021 • by Marc Airhart

The first theoretical model of condensin, a molecular machine involved in packing and unpacking chromosomes, accurately reproduces all known experiments with just two parameters.

Illustrations of a molecule in two states, open and closed

To scrunch a chromosome (green), a condensin molecule opens and closes like a pair of fingers (light blue) connected by a hinge (dark blue).


A microscope image of a strand of DNA with a loop in it

Click to download video: https://www.science.org/doi/suppl/10.1126/science.aar7831/suppl_file/aar7831s4.mp4

In a 2018 paper in Science, researchers from Delft University described how they tethered two ends of a DNA molecule to a surface, stained it with a glowing dye, and added condensin. In this video, you can see a loop of DNA grow (get brighter) as condensin scrunches up the strand of DNA.

Earlier experiments showed that condensin reels in the chromosome, scrunching sections up into thousands of loops, causing the chromosome to look less like a long, straight noodle and more like a dense ball of spaghetti. Condensin looks a bit like two fingers joined together by a hinge at the base. To reel in a section of chromosome, the fingers pull inward toward the base.

The new model built by Takaki, which accurately reproduces the speed of loop formation from those earlier experiments on chromosomes, uses just two parameters: the distance between the finger tips and base of condensin as it opens and closes, and the rate that condensin consumes energy. Scientists often describe theories that are both simple and powerful as being beautiful.

"As theorists, we're constantly looking for beautiful theories," said Thirumalai, the Marvin K. Collie-Welch Regents Chair in Chemistry and senior author of the paper. "Sometimes it works, sometimes it doesn't. In this case, it does."

Chromosomes are a vital element in every cell; they contain the genetic information for building all the proteins in the body and maintaining all the normal functions of life. When condensin doesn't perform its role in packing and unpacking chromosomes correctly, the organism usually dies early in development. Meanwhile, some mutations can lead to various forms of cancer, most commonly T-cell lymphoma.

"This packing and unpacking has to happen for many, many cycles during the life of a cell," Thirumalai said. "If it doesn't work correctly, that has big impacts downstream. It's like when your computer's hard drive crashes, you're in big trouble. Fortunately, we have systems in the cell that usually keep that from happening."

The paper's other authors are graduate student Atreya Dey and postdoctoral researcher Guang Shi.

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