DNA
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Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. )
The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection.
For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications.
The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin.
“In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.”
Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones.
“This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said.
By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy.
The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP.
“We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.”
The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2.
Profile
-Professor Ji-Joon Song ( www.song-kaist.org)
Associate Professor
Department of Biological Sciences
Email:songj@kaist.ac.kr
KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
-Dr. Carol Cho
Department of Biological Sciences
The Research Center for Natural Sciences
KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
2020.01.07 View 1204 -
Micropatch Made of DNA
Researchers reported the fabrication of microstructure arrays of DNA materials using topographic control. This method provides a platform for forming multiscale hierarchical orientations of soft and biomaterials using a process of simple shearing and controlled evaporation on a patterned substrate. This approach enables the potential of patterning applications using DNA or other anisotropic biomaterials.
DNA is one of the most abundant biomaterials found in all living organisms in nature. It has unique characteristics of fine feature size and liquid crystalline phase, enabling to create various kinds of microstructure DNA arrays. Based on these characteristics, DNA has been used as a building block for “origami” and textile art at the nanometer scale.
A KAIST research team led by Professors Dong Ki Yoon and Hyungsoo Kim fabricated a DNA-based micropatch using the “coffee ring effect” and its multi-angle control technology, which was published online in Nature Communications on June 7.
The research team used cheap DNA material extracted from salmon to realize the micropatch structure with well-aligned knit or ice cream cone shapes. When the DNA material in an aqueous solution is rubbed between two solid substrates while water is evaporating, DNA chains are unidirectionally aligned to make a thin film such as in LCD display devices. The DNA chains can make more complex microstructures such as knit or a texture with ice cream cone shapes when the same procedure is carried out in topographical patterns like microposts (Figure 1). This can be applied to make metamaterials by mixing with functionalized gold nanorods to show plasmonic color.
Plasmon resonance is a phenomenon in which electrons vibrate uniformly on the surface of a substrate made of metal, reacting only to light that matches a specific energy to enhance the clarity and expression of colors. For this, the most important factor is the orientation in which the gold nanorods align. That is, when the rods are aligned side by side in one direction, the optical and electrical characteristics are maximized. The research team focused on this point and made the DNA micropatch as a frame to orient the gold nanorods in a unique shape and fabricated a plasmonic color film (Figure 2).
Professor Yoon said this study is meaningful in that it deals with the evaporation phenomenon, which has not been studied much in the field of polymers and biopolymers in terms of basic science. He explained, “This will also help maximize the efficiency of polymeric materials that can be orientated in coating, 2D, and 3D printing applications. Furthermore, DNA that exists infinitely in nature can be expected to have industrial application value as a new material since it can easily form complexes with other materials as described in this study.”
(Figure 1. The DNA micropatch using topographic control. (a) The experimental scheme.
(b) Enlarged image of (e). (c-e) Different micropatches made of DNA using different shearing directions.)
(Figure 2. The knit-like structures made of DNA-gold nanorod complex. (a,b) Optical
and polarized optical microscopy images. (c-f) Plasmonic colors reflected from aligned DNA-gold nanorod complex depending on the sample rotation.)
2019.07.01 View 25837 -
JETS Conference 2017
KAIST and four science and technology research universities in Korea co-hosted a technology start-up fair, the 2017 JETS (Job, Exhibition, Tech Forum, and Startup) Conference January 19 ~20 in the Ryu Geun-chul Sports Complex at KAIST.
Korea’s major science and technology research universities, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Gwangju Institute of Science and Technology (GIST), Pohang University of Science and Technology (Postech), and Ulsan National Institute of Science and Technology (UNIST), held the event in a collaborative effort to educate, inspire, and connect young entrepreneurs, especially those who will launch technology start-ups.
The conference brought entrepreneurs and innovators together who seek ways of working with and supporting start-ups and for their sustainable growth. It also drew aspiring young students and researchers from universities and the government-funded research institutions who are in the process of commercializing their technology. Students from each university’s industry-academia cooperation program who incubated their technology and ideas were key contributors.
At the Tech Forum, entrepreneurship and technology consultation specialists including Joe Jasin, managing director at DNA Investment Partners in the US, the founder of Cyworld Dong-Hyung Lee, and Professor Hawoong Jeong, a complex bio-network specialist from the Department of Physics of KAIST lectured on the ecosystem of start-ups and its trends and development.
The Dean of University-Industry Cooperation at KAIST Joongmyeon Bae said, "We organized this event in collaboration with four major research universities to further encourage technology start-ups from young students and help their ideas and technology bear fruit. We will continue to strive to create an ecosystem of start-ups which works efficiently.”
(Above photo: Founder of the Cyworld, Dong-Hyung Lee gives a lecture at the Tech Forum. Below photo: Students visit exhibition booth of each participating institution.)
2017.01.20 View 2747 -
DNA based semiconductor technology developed
Professor Park Hyun Gyu’s research team from the Department of Chemical and Biomolecular Engineering at KAIST has successfully implemented all logic gates using DNA, a feat that led the research to be published as the cover paper for the international nanotechnology paper "Small".
Even with the latest technology, it was impossible to create a silicon based semiconductor smaller than 10nm, but because DNA has a thickness of only 2nm, this could lead to the creation of semiconductors with groundbreaking degrees of integration.
A 2 nm semiconductor will be able to store 10,000 HD movies within a size of a postage stamp, at least 100 times more than the current 20nm semiconductors.
DNAs are comprised of 4 bases which are continually connected: Adenine (A) with Thymine (T), and Guanine (G) with Cytosine (C).
For this research, the team used the specific binding properties of DNA, which forms its helix-shape, and a circular molecular beacon that has fluorescent signaling properties under structural changes.
The research team used input signals to open and close the circular DNA, the same principle that is applied to logic gates in digital circuits.
The output signal was measured using the increase and decrease of the fluorescent signal from the molecular beacon due to the opening and closing of the circular DNA respectively.
The team overcame the limited system problems of the existing logic gates and managed to implement all 8 logic gates (AND, OR, XOR, INHIBIT, NAND, NOR, XNOR, IMPlCATION). A multilevel circuit that connects different logic gates was also tested to show its regenerative properties.
Professor Park said that “cheap bio-electric devices with high degrees of integration will be made possible by this research” and that “there will be a large difference in the field of molecular level electronic research”
Mr. Park Gi Su, a doctoral candidate and the 1st author of this research, said that “a DNA sequence of 10 bases is only 3.4nm long and 2nm thick, which can be used to effectively increase the degree of integration of electronic devices” and that “a bio computer could materialize in the near future through DNA semiconductors with accurate logic gates”.
XOR Gate: The output signal 1 comes through the open circular DNA when either input DNA A or input DNA B is present. When both inputs are not present, the flourescent signal does not come through
2012.09.27 View 5684