Key to packaging DNA into a millionth of its original size

When threads or earphone wires get twisted in confined locations, they are easily tangled. When a cell splits, our body's long and loose DNA is compressed into one-millionth-sized rod-shaped chromosomes. If a cell divides with DNA that is nearly two metres long, there is a chance of genetic material being damaged or lost. As a result, chromosomal condensation is required for accurate transmission of genetic information.

Professor Changyong Song and Dr. Daeho Sung from the Department of Physics at POSTECH, as well as Professor Jae-Hyung Jeon and Ph.D. candidate Chan Im from the Gwangju Institute of Science and Technology, used the X-ray from the third-generation synchrotron facility to analyse human chromosomes in their clustered state. The findings were reported in the Proceedings of the National Academy of Sciences with a nanometer-scale resolution (PNAS).

For more than a half-century, researchers have been baffled by the packing mechanism that condenses chromosomes to one-millionth their original size without tangling, as well as the 3D structure that enables this. However, seeing the chromosomes in their natural state has been difficult. The researchers had to rely on merely detecting a few chromosomal components or inferring their condensed state from their uncoiled state.

The 3D structure of chromosomes was validated using coherent X-rays generated by a 3rd generation synchrotron facility after the hydrated chromosomes were swiftly frozen and kept in a cryogenic state. Unlike traditional approaches that thinly sliced or coloured the chromosomes, our discovery revealed their structure in their natural state.

The findings confirmed that chromosomes are generated in a fractal structure rather than the hierarchical structure previously suggested by earlier studies. In addition, a physical model of the chromosomal packing mechanism was presented.

Professor Changyong Song remarked, "We have determined the 3D structure of chromosomes using high-resolution photographs at the nanometer-scale using coherent X-rays from the synchrotron." "Not only does the technique used in the study provide the key to understanding genetics — the essence of all living things — but it also provides the key to uncovering the 3D structures of other materials, such as viruses, whose exact structure is critical."

A new study sheds light on the Earth's origins of life.

A Rutgers-led research has uncovered the structures of proteins that may be responsible for the genesis of life in the primordial soup of old Earth, answering one of biology's most profoundly unresolved riddles. The findings were published in the journal Science Advances.

The researchers looked at how simple, non-living components could have given rise to primitive life on our planet. They wondered what characteristics constitute life as we know it, and came to the conclusion that anything living would have needed to collect and consume energy from sources like the Sun or hydrothermal vents.

In chemical terms, this means that the ability to shuffle electrons is essential for life. Because metals (think conventional electrical lines) are the best materials for electron transmission and proteins are responsible for the majority of biological activities, the researchers chose to investigate the combination of the two — proteins that bind metals.

They analysed all current protein structures that bind metals to determine whether there were any similar traits, assuming that these shared features existed in ancestral proteins and were diversified and passed down to generate the diverse range of proteins we see today.

Understanding how new folds arose from previously existing ones is important in protein evolution, so the researchers devised a computational method that revealed that the vast majority of currently existing metal-binding proteins are similar, regardless of the type of metal they bind to, the organism from which they came, or the function assigned to the protein as a whole.

Yana Bromberg, a professor in the Department of Biochemistry and Microbiology at Rutgers University-New Brunswick, said, "We saw that the metal-binding cores of existing proteins are actually comparable, even though the proteins themselves may not be." "We also discovered that these metal-binding cores are frequently composed of repeating substructures, similar to LEGO blocks." Surprisingly, similar blocks were discovered in other parts of the proteins, not just the metal-binding cores, as well as in many additional proteins not included in our analysis. Our findings suggest that rearrangements of these small building blocks may have shared a single or limited number of common progenitors, giving rise to the current diversity of proteins and their activities.

Bromberg's research focuses on interpreting the DNA blueprints of life's molecular machinery. "We have very little information on how life started on this planet, and our work adds a previously unavailable answer," he added. "This explanation may also be useful in our hunt for life on other planets and planetary bodies. Our discovery of the unique structural building blocks could be useful for synthetic biology initiatives, in which scientists try to create new proteins that are specifically active."

Researchers from the University of Buenos Aires were also involved in the NASA-funded investigation.