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Research Finds Evidence of an Overlooked Force That Keeps DNA Stable

New research suggests the presence of another force, even stronger than a hydrogen bond, that holds our DNA together. First discovered in the 1950s, the iconic double helix structure of our genetic material is still a mystery. Looking like a twisted ladder, the rungs in the middle form nitrogen base-pairs, held together by hydrogen bonds, one of the strongest intermolecular attractions around. These ultra-strong links that connect both sides, are frequently described as the major stabilizing force in DNA. But maybe there’s another, a more important factor at play. DNA replication typically occurs with the help of several enzymes, which ‘unzip’ DNA molecules by breaking their hydrogen bonds. It seems, though, that’s not the only way to destabilize the double helix.

Researchers at the Chalmers University of Technology in Sweden tested the DNA in an environment more hydrophobic than normal to show for the first time that this water-repelling force is sufficient to unravel the double helix all on its own.

The authors conclude, “The main stabiliser of the DNA double helix is not the base-pair hydrogen bonds but coin-pile stacking of base pairs, whose hydrophobic cohesion, requiring abundant water, indirectly makes the DNA interior dry so that hydrogen bonds can exert full recognition power.”

This implies that as DNA base pairs are naturally water-repelling, in a normal water solution, they in a way stack together to protect from their surroundings almost like a colony of huddling penguins. Breaking such groupings apart entails the opposite effect. By progressively adding a hydrophobic solution of polyethylene glycol, often used in cars as antifreeze, the team has demonstrated that DNA loses its structure when its surroundings go from water-loving to water-repelling.

It’s yet unclear if enzymes in nature behave similarly, but given previous research on the topic, the team opines it is a distinct possibility.

Chemical engineer and lead author Bobo Feng explains, “Cells want to protect their DNA, and not expose it to hydrophobic environments, which can sometimes contain harmful molecules. But at the same time, the cells’ DNA needs to open up in order to be used.”

Feng and his colleagues suggest that a normal cell keeps its DNA in a water solution up until it wants to read, copy or repair its DNA. Only then does the cell produce a more hydrophobic environment, through the use of enzymes with a function similar to polyethylene glycol.

Steven Brenner, a molecular biophysicist at NASA, told ScienceAlert that this was a significant discovery that establishes a new way enzymes might ‘melt’ the double helices of DNA for transcription or repair. Still, he cautions, the narrative by many mainstream media outlets covering this paper is not entirely accurate.

Regardless of what many are reporting, he says the results do not submit that hydrogen bonds are unimportant for DNA formation but that hydrophobic forces also play a vital role. Apparently, this is hardly a new concept. Models that comprise hydrophobic interactions in the double helix can be traced back to at least the 1990s, and today, there are complete labs devoted to this path of research.

Back in 1997, scientists even began questioning the concept that hydrogen bonds alone can hold the two strands of a DNA double helix together. The textbook explanation proved inadequate, and years later, a 2004 study submitted that hydrogen bonding was not required for the stability of base pairs.

A few years ago, a 2017 study demonstrated that a lack of complementary hydrogen bonds doesn’t actually bother cells and that synthetic bases are successfully transcribed and translated nonetheless, using only hydrophobic forces. Collectively, these results propose that perhaps the forces we’ve observed in nature aren’t the only ones in control of the double helix.

Biochemist Floyd Romesberg, an author of the 2017 paper, said, “It would be very easy to say complementary hydrogen bonds are what define DNA and RNA. But we’ve found that forces other than hydrogen bonding can productively participate in every step of information storage and retrieval.”

Yet, there are still limits to the conclusions derived from these models.

Benner told ScienceAlert, “One of the sad lessons of physical organic chemistry from the last century is that efforts to separately model the behaviour of molecules as the consequence of different factors , tells you more about the chemist doing the modelling than it tells you about the molecules themselves.”

These frameworks, for example, can either be assessed on their ability to merely explain DNA or on their ability to essentially make it. For his part, Benner believes the latter analysis is more objective as explanations on their own can every so often just convince us we understand what’s going on.

He argues, “If however, our models actually allow us to make things, then they must really have some reality behind them”.

Finally, Benner surmises that both hydrogen bonding and hydrophobicity have proved essential in making natural DNA, and the double-pronged model is currently used both in human medicine and in NASA’s search for alien life.

The new research, published in PNAS, adds to this knowledge by providing a possible biological mechanism for this process.

Feng says, “Nobody has previously placed DNA in a hydrophobic environment like this and studied how it behaves, so it’s not surprising that nobody has discovered this until now”.

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