Dynamic twists and loops can allow DNA to regulate its function


Double stranded DNA fragment. Credits: Vcpmartin / Wikimedia / CC BY-SA 4.0

When they think of DNA, they visualize a chain-like double helix structure. In reality, the intracellular DNA double helix is ​​supercoiled and trapped in a loop. This supercoiling and loop is known to affect all aspects of DNA activity, but it’s unclear how this happens.

Published in the journal Nature Communication, Studies by researchers at Baylor College of Medicine show that superbugs and curls can be transmitted Mechanical stress Along the DNA backbone. Stress can promote separation of strands Double helix Expose DNA bases in specific remote locations. This can facilitate repair, replication, transcription, or other aspects of DNA function.

“DNA preserves the genetic information of cells in a stable and protected form, making them easily accessible for their activity to continue,” said the corresponding author of Molecular Virology and Microbiology of Baylor. A Dr Lynn Zequiedrich, President Kyle and Josephine Morrow, said. “Organisms achieve this seemingly paradoxical goal by storing DNA in supercoiled loops. Current research is exploring how superbobins and loops regulate DNA activity. “

Zechiedrich and his collaborators began by creating pieces of supercoiled DNA that would be present in living cells. They took a short, linear DNA double helix and twisted it once, twice, three or more times in the direction of rotation of the double helix (positive supercoil) or against it (negative supercoil). .. Then we connected the two ends to form a loop.

“so Previous searchWe used electronic cryotomography (cryo-ET) to study the 3D structure of supercoiled minicircles. It is an imaging technique that produces a high resolution 3D view of large molecules. ”“ We observed a surprisingly wide variety of mini circle shapes, depending on the particular supercoil level. Lots of shapes that we have observed. Contains strongly curved DNA. This observation was unexpected. “

The model was unexpected because it showed the supercoiled DNA circle behaving like a twisted rubber band.

“We found that the supercoiled looped DNA suddenly comes out of the sharp edges and destroys the double helix instead of gently bending,” says Zechiedrich. “The opening exposes that particular DNA code and makes it accessible to proteins looking for a particular sequence that interacts with DNA. For example, it repairs DNA or makes a copy of it.

“Another important discovery is the idea of ​​’action at a distance’,” said Dr Jonathan M. Fogg, senior researcher and lead author at the Zechiedrich Institute. “The effects of supercoiled stress at one site in the loop can be transmitted to distant sites along the DNA backbone. For example, if one site leans heavily, the second site is far from the first site. The site also leans heavily. Linear DNA does not capture this phenomenon, but our supercoiled minicircles reveal these dynamic properties of DNA found in cells. “

These results suggest a new perspective on how DNA activity is regulated. The current idea is that a specialized protein interacts with DNA to separate the segments of the double helix. This double helix segment, for example, must be replicated or transcribed into RNA to produce a protein.

“We have shown here that we do not need proteins to access DNA. We can make it accessible by itself, ”Zechiedrich said.

“Our cells create many complex processes to manage the storage and use of DNA, and the shape of that DNA affects them all,” said the Faculty of Pharmacology and Chemical Biology. Co-author Allison Judge, a graduate student, said.

“Our results provide new insight into what governs the shape of DNA,” said co-author Eric Stricker, a graduate student in pediatric oncology. “We suggest that these new DNA shape variations could have potential applications in nanotechnology such as gene therapy.”

“Our research turns DNA from passive biomolecules into active biomolecules,” said co-author Hildachan, a graduate student of the Medical Scientist Training Program. “Our results are future studies of how DNA can use its shape to control accessibility to specific sequences in various situations, such as a drug, infection, or response at points in the cell cycle. Stimulates. “

The first video showing the “dance DNA” propeller developed by scientists

For more information:
Supercoiling and looping facilitate accessibility of DNA bases and coordination between distant sites. Nature Communication (2021). DOI: 10.1038 / s41467-021-25936-2

Quote: Dynamic twists and loops allow DNA to regulate its function (September 28, 2021). Obtained from https://phys.org/news/2021-09-dynamic-loops-enable-dna-modulate.html on September 28, 2021

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