Genome complexity: DNA 3D layer of gene control (Introduction)

by David Turell , Friday, May 12, 2017, 20:51 (2540 days ago) @ David Turell

Another article on the importance of the 3-D relationships of DNA and gene expression:

https://www.quantamagazine.org/20160105-supercoiled-dna/?utm_source=Quanta+Magazine&...

"double-helix DNA is further wrapped into complex shapes that can play a profound role in how it interacts with other molecules. “DNA is way more active in its own regulation than we thought,” said Lynn Zechiedrich, a biophysicist at Baylor College of Medicine and one of the researchers leading the study of so-called supercoiled DNA. “It’s not a passive [molecule] waiting to be latched on to by proteins.”

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"Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Additional work by David Levens, a biologist at the National Cancer Institute, has shown that transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read.

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"DNA rarely gets to relax. It’s subject to a continual onslaught of molecules that bind it — the enzymes that untangle, unwind and then replicate DNA; the molecules that mark which genes are active and which are silent; and the proteins that pack the lengthy molecule into a manageable size. All of these molecules contort DNA into new shapes, blocking it from the repose of the simple double helix.

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"How the cell decides to activate a certain gene, for example, involves a complex assembly of molecules in the right place at the right time.

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"Levens and collaborators found that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself effects how the molecule responds to supercoiling. For example, the researchers identified a specific sequence of DNA that’s prone to opening when stressed, like a weak spot in an old inner tube. The segment acts as a sort of chemical cruise control; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA.

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"supercoiling can split the two strands of the helix, rotating the DNA bases that normally lie inside the helix to the outside, a phenomenon known as base flipping. Other simulations show that twisting a bit more flips out additional bases, creating a bubble of inside-out DNA. Zechiedrich theorizes these bubbles might provide trigger points for replication or gene expression. This challenges the standard view, in which proteins latch onto DNA and launch these events. “Who’s driving the bus in cellular metabolism?” said Sumners. “It’s a very dynamic process — DNA and proteins each influences how the other acts and reacts.'” (my bold)

Comment: Yes, who is driving the bus? All of these molecules, DNA and others in the cell, act as if they were thinking workers in a human factory turning out a product. They must work on information that coordinates their movements. Every cell in the human body or other organisms is doing this at every moment of their lives. Too complex for chance. It requires mental planning.