A New Insight Into How DNA Is Held Together by Hydrophobic Effects

For DNA to be read, replicated or repaired, DNA molecules must open themselves. This happens when the cells use a catalytic protein to create a hydrophobic environment around the molecule. Illustration Credit: Yen Strandqvist/Chalmers University of Technology

Note: This article and headline were updated on September 29, 2019, to clarify the impact of the research.

Researchers at Chalmers University of Technology, Sweden, have discovered a new aspect to the way that DNA binds itself, and the role played by hydrophobic effects. They show how small changes in water properties can delicately control the binding process. The discovery opens doors for new understanding in research in medicine and life sciences. The research is presented in the journal PNAS.

DNA is constructed of two strands, consisting of sugar molecules and phosphate groups. Between these two strands are nitrogen bases, the compounds which make up organisms’ genes, with hydrogen bonds between them. Those hydrogen bonds have sometimes been seen as crucial to holding the two strands together.

But now, researchers from Chalmers University of Technology show that the secret to DNA’s helical structure may be that the molecules have a hydrophobic interior, in an environment consisting mainly of water. The environment is therefore hydrophilic, while the DNA molecules’ nitrogen bases are hydrophobic, pushing away the surrounding water. When hydrophobic units are in a hydrophilic environment, they group together, to minimise their exposure to the water.

“We believe that the cell keeps its DNA in a water solution most of the time, but as soon as a cell wants to do something with its DNA, like read, copy or repair it, it exposes the DNA to a hydrophobic environment.” — Bobo Feng

The role of the hydrogen bonds, which have sometimes been seen as crucial to holding DNA helixes together, appear to be more to do with sorting the base pairs, so that they link together in the correct sequence.

The discovery is crucial for understanding DNA’s relationship with its environment.

Bobo Feng, Postdoc, Chemistry and Chemical Engineering, Chalmers University of Technology. Credit: Johan Bodell/Chalmers University of Technology

“Cells want to protect their DNA, and not expose it to hydrophobic environments, which can sometimes contain harmful molecules,” says Bobo Feng, one of the researchers behind the study. “But at the same time, the cells’ DNA needs to open up in order to be used.”

“We believe that the cell keeps its DNA in a water solution most of the time, but as soon as a cell wants to do something with its DNA, like read, copy or repair it, it exposes the DNA to a hydrophobic environment.”

Reproduction, for example, involves the base pairs dissolving from one another and opening up. Enzymes then copy both sides of the helix to create new DNA. When it comes to repairing damaged DNA, the damaged areas are subjected to a hydrophobic environment, to be replaced. A catalytic protein creates the hydrophobic environment. This type of protein is central to all DNA repairs, meaning it could be the key to fighting many serious sicknesses.

Understanding these proteins could yield many new insights into how we could, for example, fight resistant bacteria, or potentially even cure cancer. Bacteria use a protein called RecA to repair their DNA, and the researchers believe their results could provide new insight into how this process works – potentially offering methods for stopping it and thereby killing the bacteria.

In human cells, the protein Rad51 repairs DNA and fixes mutated DNA sequences, which otherwise could lead to cancer.

“To understand cancer, we need to understand how DNA repairs. To understand that, we first need to understand DNA itself,” says Bobo Feng. “We have shown that DNA behaves totally differently in a hydrophobic environment. This could help us to understand DNA.”

More information on the methods the researchers used to show how DNA binds together:

The researchers studied how DNA behaves in an environment which is more hydrophobic than normal, a method they were the first to experiment with.

They used the hydrophobic solution polyethylene glycol, and step-by-step changed the DNA’s surroundings from the naturally hydrophilic environment to a hydrophobic one. They aimed to discover if there is a limit where DNA starts to lose its structure, when the DNA does not have a reason to bind, because the environment is no longer hydrophilic. The researchers observed that when the solution reached the borderline between hydrophilic and hydrophobic, the DNA molecules’ characteristic spiral form started to unravel.

Upon closer inspection, they observed that when the base pairs split from one another (due to external influence, or simply from random movements), holes are formed in the structure, allowing water to leak in. Because DNA wants to keep its interior dry, it presses together, with the base pairs coming together again to squeeze out the water. In a hydrophobic environment, this water is missing, so the holes stay in place.

Reference: “Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects” by Bobo Feng, Robert P. Sosa, Anna K. F. Mårtensson, Kai Jiang, Alex Tong, Kevin D. Dorfman, Masayuki Takahashi, Per Lincoln, Carlos J. Bustamante, Fredrik Westerlund and Bengt Nordén, 27 August 2019, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.1909122116

Note: This article and headline were updated on September 29, 2019, to clarify the impact of the research.

CancerChalmers University of TechnologyDNA
Comments ( 45 )
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  • Dr Susila Marimuthu PhD

    Very interesting and a research that promises future progress to end nasty cancer.

  • Linus P. Franklin

    The perspective shared by Chalmer’s public-relations article doesn’t “hold water”, as the researchers haven’t actually challenged the role of hydrogen-bonding. The spiraling array of these polarized groups keeps the hydrophobic grooves from clumping together, which would render the DNA molecule useless. The hydrogen-bonds are also the reason that the strands can easily unzip – the necessity of which has “not escaped our notice” since 1953. Therefore, hydrogen bonding is the key to DNA’s double helical structure and function, not the hydrophobic planes. Perhaps the group would be better received by focusing their hydrophobic research within the single DNA strands involved in meiosis.

  • Yo mama

    More studies will prove the scientists are making headway toward the truth.
    Not so much for right wing bible thumpers…nut jobs…

    • Rev Dr Maistry

      You haven’t read the Bible then sir? Water is the foundation of all the living.It stored memory. It is the great divide between this world and the other side. Hydrogen surrounded by a water ( bubble) is the beginning of a star. All it needs is the right base frequency to pass through it( A voice) and it bursts into a star emitting every known element. Yes, read the bible not with a predisposition but open mind. Not as a religious nut but a primed mind. Quantum science is also there. God is real. Science is just starting to catch up. Blessings

      • blessings

        True in some ways but wrong in so many others.

  • Weezy

    Quran said that every living thing is made of water (verse 21:30)

    • Let there be light.

      and Thales of Miletus said the same thing… just a thousand years earlier.

    • S

      Egypt is the gift of the Nile (water) 4000 years before Allah’s discovery

    • snappleisthebest

      Thanks for the snapple cap tidbit.

  • Leon Zhang

    No surprise at all. Seven years ago a biophysicist from ASU called to stop the support of research on methylations in a meeting, which he believes that the modification just change the hydrophilicity and the package of DNA change correspondingly.

  • Ifraz Sheikh

    It is very complex to understand human mechanism

  • Daniel SmartyPants

    Wow!!!!!!! Now we can reelect Trump!

  • Just me

    The title is really bad, “Scientists were wrong….”. It was a group of scientists that proposed the alternative hypothesis. This sort of title plays into the current theme that scientists are just wrong about everything so we don’t need to pay attention to what they say, such as burning hydrocarbons produces carbon dioxide. Please be more careful.

    • sensationalistnonsense

      Excellent point. Journalists and the public, pay attention.

  • Kirk Wilhelmsen, MD-PhD

    I was taught that the exclusion of water by the stacking of hydrophobic basepairs was the driving force that held DNA strands together as an undergraduate majoring biochemistry at UCSD 42 years ago. It is still true that base sharing effects how strands base pair. The negative charge of the phosphates on the backbone would repel the two strands from base-pairing if it were not for the exclusion of water from the stacking of greasy basepairs. There must be more to the original article than described by this news article.

  • Mike Holloway

    Deng, and/or the “science reporter”, is being unnecessarily misleading, presumably to make the story exciting. Never in the history of biochemistry were biochemists unaware of hydrophobicity. Charges and interaction with water is pretty much what the whole field has always been about. No one has ignored hydrophilicity in any biochemistry study of DNA-protein interaction, ever. Guess we have to look up the paper to find out what it really is about.

    • Uday

      Did you even read the article? It acknowledges that people have studied DNA in hydrophilic environments forever. But the explanation for helix stabilization was also based on a hydrophilic property – hydrogen bonding. When you place it in a variety of hydrophobic environments, this idea unravels in ways not previously observed.

  • JJ

    The news is a oversell of the paper. The PNAS paper only showed hydrophobic stacking helps hold the structure together, instead of undermining the contribution from DNA base pairs.Hydrobic stacking provides 2-3kJ/mol bond strength whilst the base pair H-bonding provides ~20kJ/mol stabilization for each pair. BTW, in the PNAS paper experiment design, exposing DNA to a hydrophobic environment would disrupt both hydrophobic stacking and H-bond. You really can’t distinguish between the two based on authors experimental data. Would be nice to see a XRD data but oh well.

  • BioMajor

    Really interesting! Can’t wait to see where their research heads to. Hopefully this allows for further expansion into biology and epigenetics! Also, to one of the commentors here; it’s DNA. It can’t vote, and doesn’t care about anyone’s political opinion, so please keep politics to yourself and in the appropriate setting 🙂

  • Phil

    I’m pretty sure I learned this in more than one undergrad chemistry class. Not sure how this is news.

  • James R Walker

    A quote from the paper’s first paragraph:

    …we wish to refer to 3 seminal contributions made more than 60 y ago… …that the DNA double helix is stabilized mainly by hydrophobic and dispersive stacking interactions.

    How about you read the paper before you write a headline?

    • Dr Patel

      Interesting that you truncated the sentence. Why???

      “the DNA double helix is stabilized mainly by hydrophobic and dispersive stacking interactions and less by the hydrogen bonding between matched bases that most textbooks still refer to”

      That wasn’t the first paragraph either. Count much?

      The first sentence states:

      “The main stabilizer 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.”

      Go to https://en.wikipedia.org/wiki/DNA

      What does it say repeatedly? That hydrogen bonds bind the two strands. It doesn’t even contain the word “hydrophobic.”

  • g raviteja

    Yes you are correct …. If they are hydrophilic the situation is different… Some of the components get dissolved in water…

  • Roland Dunbrack

    This is not at all what the article says. The idea that hydrophobic forces hold the helix together while the hydrogen bonds provide the sequence specificity is very old; this study does not add to that.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360284/

    Instead, this study proposes that protein enzymes that work on DNA may take advantage of the hydrophobic effect to function. Very different than “cientists Were Wrong About DNA – It Is Actually Held Together by Hydrophobic Forces”.

  • YT

    Not news and very misleading title. Also, not doing justice to the excellent scientists involved.

    Reflecting contemporary trends, where journalists must sensationalize everything (and, ironically, moving away from the truth by doing so).

  • Kevin

    Journalists should take a course in reporting on science and technology. Then it can find its way to media culture. To report on science to report honestly, the truly new things in contrast to the old and current, on what it has to offer rather than highlight old information and fail or be ignorant to mention that, to get views for their article. Humanity is and should be willing to be informed of genuine knowledge and deserve media that serves to inform rather than serve their own interests. If journalists look at movies and events so meticulously like lawyers, historians and filmmakers despite experience or being as informed, they should look at science as closely as they can, with respect to their knowledge, to give a condensed representative picture, easily in just as simple(however so) and as much words. The media has the ear and trust of the public and the opportunity to educate them.
    A bonds to T and U and G to C because those are the only partners they can H bond, the only way nucleotides can find and bond to each other, and the collective strand is kept together by hydrophobic forces. And we know that, but what we KNOW is…_____ (No opinion but a truthful frame of facts over time leading to this new finding)

  • MJM

    I am more than pleased to see how scientists maintain scientific integrity and adamantly go after misleading and misguided reports of scientific works. I believe in science and the comments I have read here justify that belief. Thank you all.

  • Tyree L Stehle

    I know that water is the key to life in all areas. Blood is to be studied more than ever. The life is in the blood. Yes, that’s in the bible. Keep mocking God, for you have no gifts of our Lord. Bible thumpers you make fun of, but I know for a fact that you have no idea how your soul was created and you cannot explain why us humans have dreams or why we dream in our sleep. Answer that if you dare. God created us all, we each are different in so many ways, yet so much alike in others, therefore what works for some, will not be an overall cure for others. That’s just life, again, life is in the blood.

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    • anon anon

      Lol

  • Every knee shall bow

    “Not so much for right wing bible thumpers…nut jobs…”?
    You’re in for a big surprise! I was an atheist until 3 years ago. God revealed himself to me through supernatural events. I even had a demonic spirit go inside of me. God is very real. Just because you don’t believe in him doesn’t change the truth. You believe in an extremely intelligently designed universe that accidentally created itself. Atheism is absolutely ridiculous. Science doesn’t disprove God, it only proves him. Especially “theories” that atheists make up to support their agenda. There is not one transitional fossil to support macro evolution. You believe an intelligently designed world created itself from nothing, you are the NutJob. And when you die, you will go before God Almighty, and you will bow and confess that Jesus Christ is Lord! That you can bet.

    • the true god does not make anyone bow

      No scientist is claiming that God does not exist. Just that it is not the one in your delusion, Jesus Christ or his father. But you’re right that science only proves God, that wonderfully intelligent cosmic spirit. The true god does not make anyone bow – they love you the way you love them.

  • shmoe

    how come scientist only show pics of broken dna. thay are not studing dna for any good reason wast of money and ther own brains time i hope the reserch back fires on ther asses.

  • Jan-Philipp Denger

    What phases me is that the article refers to PEGs as hydrophobic.

  • ScottC

    Terrible article. As point out by others the headline is not correct, and DNA being held together by the hydrophobic effect has been known for decades. Try reading the paper first or even better running the article past the authors for feedback before publication. You have disrespected these fine researchers. I guess most of your readers won’t notice such disregard judging from the nut job comments below.

    • Phil Wilson

      Did you even read the quotes from the lead researcher in the article? In what way do they differ from the article or headline?

      What you see in these comments is the Dunning–Kruger effect in full. A bunch of people that had one biochem course in undergrad thinking they know more than a postdoc researcher.

  • Judy

    So if water makes DNA binds closer together to protect itself from water while reparing or changing itself leaves it open to damage can we infer that drinking more water helps protect DNA? Over simplified?
    Oh OK thanks for post. Want to research more. Seemed a little …..different explanation.

  • Joe Falcone

    Dr. Parthasarathy at SUNY Buffalo Roswell Park Memorial Cancer institute taught us this in 1989, before it was cool. He insisted then the model was wrong. Kudos to you for publishing, and proving his gut instinct.

  • Bapurao Bhoge

    This scientific story is written in a such a way that it becomes a perfect example of how scientific stories should not be written!

    This is not the first time. Scientist are well aware that DNA is held together by hydrophobic forces. Please visit this article below
    Nature 399,704-708(1999).

  • MarcB

    Huh?! Base stacking has long been known to be the predominant force in nucleic acid structure…I don’t get what this article is saying.

  • Stephen K Farrand

    IN fact, we’ve been teaching this to our undergraduate Molecular and Cell Biology majors for the past 5 years.

  • Roger Rowlett

    This is not news. The role of hydrophobic association of bases in ss- and ds-DNA has been known for a long time, and amplified by Kool’s studies decades ago. My undergraduates have learned this in my classes for many years.

  • Anonymous Professor

    I’ll echo many of these comments that this article NEEDS to be taken down. This is not their discovery and in fact we have known that DNA is stabilized by hydrophobic interactions (stacking) and not hydrogen bonds for many decades – since 1962 as the PNAS paper correctly reports. This is general knowledge and is found in most textbooks (e.g. Fundamentals of Biochemsiry, 5th ed. Voet, Voet, Pratt, ch24 section 2A) and I’ve been teaching this in my classes for many years. There is indeed a commonly held misconception that hydrogen bonds hold the DNA together but the scientific community does not share this misconception. It is a rather large misrepresentation to suggest that this group has discovered this and does not do justice to the true nature of their discovery. Please hide this article until such a time as you can correct it’s content. Many internet media outlets are picking up on your reporting and copying it.

  • Dr H. M. Khala

    This study is more of the role of hydrophobic interaction in DNA helical structure and DNA associated protiens function but doesn’t effectively negate the role of hydrogen bonds in DNA structure and function which is supported by other findings such as sequence of important DNA regions.

  • Joseph Cruz

    This was really interesting