Junk DNA goodbye!: importance of arranging 3-D DNA (Introduction)

by David Turell , Saturday, November 23, 2019, 01:27 (1616 days ago) @ David Turell

There was no comment upon the last entry on 3-D DNA, and n ow an other article with a different approach, showing how loops are arranged for by cohesin:

https://phys.org/news/2019-11-groundbreaking-cohesin-molecular-motor-genome.html

"It took many decades to identify the chromosomes as strands of DNA neatly folded into loops, and even longer to realize that DNA is folded into such structures in all cells and at all times; it took until 2019 to find out how this folding is accomplished. In a paper published by the journal Science, researchers from Jan-Michael Peters' lab at the Institute of Molecular Pathology (IMP) in Vienna have demonstrated for the first time that a molecular machine actively and purposefully folds DNA via "loop extrusion," and thereby fulfills several important functions in the interphase cell.

"That the process of looping DNA is neither random nor arbitrary is evident from how evolutionarily ancient it is. Cells of all organisms perform this function, from bacteria to humans. The primeval function of the folding mechanism is still unknown, and we may never find out, but some vital tasks have been discovered in recent years. By looping DNA, distant regions on the large molecule are brought into close proximity and are able to interact. This physical contact plays an important role in gene regulation, in which DNA segments called enhancers influence which genes are active. Looping is also essential for the ability of immune cells to produce a diverse array of antibodies.

"The team involving Davidson, a senior postdoc in the Peters lab at the IMP, was able to reconstitute cohesin function in a simplified system in vitro. Thus, he could watch how single cohesin molecules rapidly extruded single pieces of DNA into loops, exactly as Mirny and others had postulated. His findings, published online on 21 November 2019, are far-reaching and change the entire perception of the genome in several ways:

"Rather than being static, the genome is a highly dynamic structure.

"The folding of genomic DNA is an actively regulated process. It involves looping the DNA molecule by way of extrusion, with many loops in constant motion.

"The looping process is mediated by cohesin, which must therefore be a molecular motor, similar to other motor proteins such as myosin, which activates muscles.

"The cohesin molecule does not just form carabiner-like rings around DNA, but must attach to DNA dynamically via several binding sites to be able to fold it. This must also be true for a related molecule, condensin, as was shown last year.

"'This is a real paradigm shift," says IMP director Jan-Michael Peters. "Earlier observations gave us some hints, but the work of Iain Davidson is now proof. In my scientific life, few other discoveries were as far-reaching as this one.'"

Comment: More about the arrangement that allows 3-D relationships between genes that are spread over a six-foot long DNA. The packing is purposeful for it allows more close relationships than would otherwise be possible. Certainly by design.