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Salk scientists solve longstanding biological mystery of DNA organization — Researchers image 3D genome in nucleus of living human cell for the first time.
Stretched out, the DNA from all the cells in our body would reach Pluto. So how does each tiny cell pack a two-meter length of DNA into its nucleus, which is just one-thousandth of a millimeter across?
[...] In the tour de force study, described in Science on July 27, 2017, the Salk researchers identified a novel DNA dye that, when paired with advanced microscopy in a combined technology called ChromEMT, allows highly detailed visualization of chromatin structure in cells in the resting and mitotic (dividing) stages. By revealing nuclear chromatin structure in living cells, the work may help rewrite the textbook model of DNA organization and even change how we approach treatments for disease.
"One of the most intractable challenges in biology is to discover the higher-order structure of DNA in the nucleus and how is this linked to its functions in the genome," says Salk Associate Professor Clodagh O'Shea, a Howard Hughes Medical Institute Faculty Scholar and senior author of the paper. "It is of eminent importance, for this is the biologically relevant structure of DNA that determines both gene function and activity."
[...] With their 3D microscopy reconstructions, the team was able to move through a 250 nm x 1000 nm x 1000 nm volume of chromatin's twists and turns, and envision how a large molecule like RNA polymerase, which transcribes (copies) DNA, might be directed by chromatin's variable packing density, like a video game aircraft flying through a series of canyons, to a particular spot in the genome. Besides potentially upending the textbook model of DNA organization, the team's results suggest that controlling access to chromatin could be a useful approach to preventing, diagnosing and treating diseases such as cancer.
"We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus," adds O'Shea. "It's the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes."
I'm by no means a geneticist. Nearly anyone can take a length of rope and coil it into a compact shape. Doing it in such a way that it can be readily uncoiled is quite another thing. So how does DNA get 'coiled up' without getting tied full of knots? Folding and unfolding, then, are critical and it seems that these researchers have made some key discoveries into this.
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(Score: 3, Interesting) by ledow on Wednesday August 02 2017, @08:44AM (2 children)
To be honest, on molecular scales are "knots" even that possible or likely? Would they be a hindrance at all?
I watched a BBC documentary the other year, where they do a bit of CGi and show you how cells works. Basically, for things like DNA, there are molecular constructs that attach to the helix (and it's a helix for a reason - ever tried to bend a ladder? The structure itself prevents certain kinds of twisting from happening) and physically traverse it by reactions between the molecules, it's like a train running on the tracks of the DNA, acting on it as it goes. That there's something in the way, or a small knot, won't hinder such processes very much. And if they hinder one strand, there are BILLIONS of other strands stored in myriads of even the tiniest of cells. One failing does not cause catastrophe, and others take up the slack or more are made.
I happen to live with a geneticist, I shall ask, but I think I know the answer. Either it's "we don't know" or "there's a mechanism to cope with that".
DNA is amazingly computer-data-like. There is actual error-detection and correction. There are end-of-buffer markers. There are replication processes that verify their copies. All kinds of things. And it happens on a physical scale, not some biological one. Which means that it's not some animal undergoing a process, it's literally just the way the physics works with the molecules involved. It's just a long ticker-tape, made to do nothing else but remain a source of data. And it does a remarkably good, accurate, and consistent job or you wouldn't be able to rely on it.
Given that there are probably billions of copies of your DNA being made today by internal processes, it works pretty reliably. That's a product of billions of years of evolution. By comparison to everything else it does, "being a shape that doesn't knot easily" is relatively trivial. Hell, my telephone handset has a cord on it in a helix format. Apart from the odd twist, it never really knots but compacts a 5m cord into a 30cm coil quite reliably. And even with the twists that it does get... if you were a spider just following the "outside track" of the cord, you wouldn't be hindered by them at all.
Pretty much, that's how DNA works.
(Score: 1, Informative) by Anonymous Coward on Wednesday August 02 2017, @02:13PM
"We don't know [entirely]" is always the answer for biological questions, but we certainly do know many regulatory mechanisms of DNA control and homeostasis.
Some other comments:
DNA coiling can be a problem and topoisomerases are proteins that will specifically relieve torsion.
DNA is routinely bent ~80 degrees by TATA-binding protein and is wrapped very tightly around histones. This is pretty impressive when you consider how stiff DNA is:
"DNA has a Young’s modulus on the order of 0.3–1 GPa, similar to hard plastic."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879068/ [nih.gov]
Also, the error rate of DNA replication in mammalian cells is usually thought to be around 10^-8 to 10^-10.
(Score: 2) by Murdoc on Wednesday August 02 2017, @05:06PM
Sure, it's called a rope ladder.