May 2, 2024

Dynamic Twists and Supercoiling Loops Can Enable DNA To Adjust Its Function

They visualize a string-like double helix structure when individuals believe of DNA. In reality, the DNA double helix in cells is supercoiled and constrained into loops. This supercoiling and looping are understood to influence every element of DNA activity, but how this takes place has actually not been clear.
Released in the journal Nature Communications, a research study by scientists at Baylor College of Medicine shows that looping and supercoiling can transfer mechanical stress along the DNA foundation. The tension can promote the separation of the hairs of the double helix at specific far-off websites, exposing the DNA bases, which might assist in repair, replication, transcription, or other elements of DNA function.

” DNA shops a cells genetic info in a safeguarded and stable kind that is easily available for the cell to bring on its activities,” stated matching author Dr. Lynn Zechiedrich, Kyle and Josephine Morrow Chair in molecular virology and microbiology at Baylor. “Organisms attain this relatively paradoxical goal by storing DNA in supercoiled loops. In the current research study, we investigated how supercoiling and looping regulate DNA activity.”
Zechiedrich and her partners began by making small pieces of supercoiled DNA, like those present in living cells. They took a brief, linear DNA double helix and twisted it when, twice, 3 times, or more, either in the instructions of the turn of the double helix (favorable supercoiling) or versus it (unfavorable supercoiling). Then they linked completions together forming a loop.
“We observed a remarkably large range of minicircle shapes depending on the specific supercoiling level. Numerous of the shapes we observed consisted of greatly bent DNA.
It was unanticipated due to the fact that the models show that supercoiled DNA circles would act more like a twisted elastic band.
” We found that supercoiled, looped DNA, rather of gently bending, all of a sudden pops out sharp edges that produce a disruption in the double helix,” Zechiedrich stated. “The openings expose that particular DNA code, making it available to proteins looking for specific sequences to engage with the DNA, for instance, to fix it or make a copy of it.”
“The results of supercoiling tension at one site of the loop can be sent along the DNA foundation to a remote website. Studying linear DNA does not catch this phenomenon, however our supercoiled minicircles reveal these dynamic properties of DNA as it is discovered in cells.”
These findings suggest a new point of view on how DNA activities are regulated. Currently, the idea is that specialized proteins engage with DNA to separate sections of the double helix that need to be duplicated, for example, or transcribed into RNA to produce a protein.
” Here we showed that no protein is needed to gain access to DNA, it can make itself available by itself,” Zechiedrich said.
” Our cells have created numerous intricate processes to handle utilizing and storing DNA, and the shape of that DNA impacts all of them,” said co-author Allison Judge, college student in the Department of Pharmacology and Chemical Biology.
” Our findings offer brand-new insights into what governs DNA shape,” stated co-author Erik Stricker, college student of pediatrics-oncology. “We propose that variations in these unique DNA shapes could have possible nanotechnology applications, such as gene therapy.”
” Our study rebrands DNA from a passive biomolecule to an active one,” stated co-author Hilda Chan, graduate student in the Medical Scientist Training Program. “Our findings promote future work on how DNA might use its shape to govern accessibility to particular series in a range of scenarios, like in action to drugs, infection or points in the cell cycle.”
Referral: “Supercoiling and looping promote DNA base ease of access and coordination among far-off websites” 28 September 2021, Nature Communication.DOI: 10.1038/ s41467-021-25936-2.
This work was supported in part by National Institutes of Health grants R56 AI054830 and R01 GM115501.

When people think of DNA, they visualize a string-like double helix structure. In reality, the DNA double helix in cells is supercoiled and constrained into loops. “Organisms attain this apparently paradoxical objective by keeping DNA in supercoiled loops. They took a brief, linear DNA double helix and twisted it once, two times, three times, or more, either in the instructions of the turn of the double helix (positive supercoiling) or against it (unfavorable supercoiling). Studying direct DNA does not record this phenomenon, but our supercoiled minicircles reveal these dynamic residential or commercial properties of DNA as it is found in cells.”