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Science And Nature

Demystifying DNA hybridization kinetics

3D-model of DNA. Credit: Michael Strck/Wikimedia/ GNU Free Documentation License

Nanoscientists and theoretical physicists at UNSW Medicine & Health’s EMBL Australia Node in Single Molecule Science joined forces to demystify the complicated mechanisms governing how quickly two matching strands of DNA can fully come togetheror hybridizeto form double stranded DNA. Their findings are published in the journal Nucleic Acids Research.

A theory was proposed some 50 years back hypothesizing that how quickly DNA strands hybridize depends upon the original contact leading to help expand binding of the string of matching bases on the DNA strandscalled nucleating interactions. As yet, this theory had never shown because of the many complexities around DNA biology.

“You can find an enormous amount of pathways by which two fully dissociated strands can bind to one another. DNA stands don’t get together right into a fully hybridized duplex immediately. At some time, only several base pairs will spontaneously join. This is exactly what a nucleating event is,” said Associate Professor Lawrence Lee who led the team of researchers from UNSW Medicine & Health, UNSW Science, and Imperial College London.

“We built a straightforward mathematic model, which only has two parameters, and asked: if we only knew just how many nucleating interactions there have been, and how stable these were, can we predict hybridization rates? And we discovered that the solution was yes,” he said.

To check this model quantitatively, the study team translated the initial hypothesis right into a they might use to measure against their experimental observations with synthetic DNA.

A/Prof Lee explains that simplicity was pivotal to the predictive power of these model.

“In case a contains way too many different parameters, it really is no longer ideal for making predictions. The main element difference to previous attempts to comprehend DNA hybridization rates was our model had few parameters and was tested against DNA sequences which should not form secondary structures,” he said.

DNA secondary structures form once the strands fold onto themselves, that may potentially obscured nucleation and binding sites.

“The idea is, if this initial small interaction is stable enough, it’ll go from there to an extremely fast zippering up of the DNA strands. If the limiting step is nucleating, then it follows that should you have significantly more nucleating states, then your DNA should hybridize faster,” said A/Prof Lee.

This discovery gets the potential to boost our knowledge of biological systems. The opportunity to predict or control the rate of DNA hybridisation, may possibly also help refine or expand the utility of nanotechnologies. With this particular new understanding, researchers can adjust the quantity and stability of nucleation interactions and, subsequently, control the rate of DNA binding. This could be achieved in lots of ways, including by altering the reaction temperature, DNA sequence, and ionic strength of the answer.

“We are able to generate high res images using DNA paintfluorescent strands of DNA used as tags for microscopybecause we have been measuring the binding and unbinding of DNA to individual molecules. But, normally it takes quite a long time to obtain data. If we’re able to rationally design sequences for DNA paint, in order that it can bind quicker, then we’re able to decrease the acquisition time for super-resolution imaging,” said A/Prof Lee.

More info: Sophie Hertel et al, The stability and amount of nucleating interactions determine DNA hybridization rates in the lack of secondary structure, Nucleic Acids Research (2022). DOI: 10.1093/nar/gkac590

Citation: Demystifying DNA hybridization kinetics (2022, July 27) retrieved 27 July 2022 from

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