Biological complexity: cell division complexity (Introduction)

by David Turell @, Thursday, February 03, 2022, 21:05 (812 days ago) @ David Turell

There is much more than the high school biology pictures and microscopes show:

https://evolutionnews.org/2022/01/dna-packing-one-of-the-supreme-wonders-of-nature/

To pack DNA into chromosome structures molecules work hand over hand:

"Cohesin and condensin are ring-shaped like donuts, leading researchers to propose that chromatin might somehow thread through their middles. But work by chromatin biologist Jan-Michael Peters of the Research Institute of Molecular Pathology in Vienna, and colleagues now shows that, in cohesin’s case at least, the protein complex grabs DNA and pulls it, passing it from one part of itself to another, much like a person hauling rope might pass it hand to hand.

"How does a molecule pass a strand hand to hand without hands or eyes? The Scientist posted an infographic to show what Peters and team found. Cohesin has a “hinge” domain that fastens onto the DNA. The hinge moves toward one of two “head” domains. The other head clamps onto the strand several base pairs down, freeing up the hinge to reset and move down to another position.

"There must certainly be more going on, because this doesn’t explain what happens to the upstream section that was reeled in. The open-access paper in Cell by Bauer et al., “Cohesin mediates DNA loop extrusion by a ‘swing and clamp’ mechanism,” says that each swing of the hinge forms a loop of DNA. Multiple loops parallel to each other begin the process of arranging the DNA for dense packing. Another player called NIPBL associates with cohesin into a cohesin-NIPBL complex during each 50-nm step, spending an ATP on each swing.

"Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, which enable chromatin folding in interphase cells. We have identified DNA binding sites and large-scale conformational changes that are required for loop extrusion and have determined how these are coordinated. Our results suggest that DNA is translocated by a spontaneous 50 nm-swing of cohesin’s hinge, which hands DNA over to the ATPase head of SMC3, where upon binding of ATP, DNA is clamped by NIPBL. During this process, NIPBL “jumps ship” from the hinge toward the SMC3 head and might thereby couple the spontaneous hinge swing to ATP-dependent DNA clamping. These results reveal mechanistic principles of how cohesin-NIPBL and possibly other SMC complexes mediate loop extrusion.

"Remarkable movies made with super-resolution atomic force microscopy show the parts of cohesin undergoing conformational changes. These hand-over-hand motions operate in the dark without eyes, using ATP for energy. They get it right every time!

***

"Researchers at Postech Physics in Korea used a synchrotron, X-rays, and cryo-electron microscopy of intact chromosomes to peer deeper into the resulting package. Their results suggested a different model of organization: a fractal model.

"The packing mechanism that condenses the chromosomes into one-millionth its size without any tanglingand the 3D structure that enables this have puzzled researchers for over a half a century. However, it has been difficult to observe the chromosomes in their native condition. The researchers had to resort to detecting only some components of the chromosomes or infer their condensed state from looking at their uncoiled state….

"Through the study, the research team confirmed that the chromosomes were formed in a fractal structure rather than the hierarchical structure stated in previous studies. In addition, a physical model showing the packing process of chromosomes was presented.

***

"How the DNA strands stay together for the process of mitosis, involving the “puzzling compaction mechanism from a DNA molecule to a chromosome and its error-free unpacking into DNA molecules again” without becoming hopelessly scrambled in the process, must count as one of the supreme wonders of nature. Look how they describe the accuracy of DNA packing despite all the interactions and motions of the adjacent molecules:

"DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints."

Comment: Everything must work together from the beginning, not piece by piece of the structure appearing in some sort of sequence. Irradicably complex by definition. Must be designed.


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