'Quadruple helix' DNA discovered in human cells

Jan 20, 2013

In 1953, Cambridge researchers Watson and Crick published a paper describing the interweaving 'double helix' DNA structure - the chemical code for all life. Now, in the year of that scientific landmark's 60th Anniversary, Cambridge researchers have published a paper proving that four-stranded 'quadruple helix' DNA structures - known as G-quadruplexes - also exist within the human genome. They form in regions of DNA that are rich in the building block guanine, usually abbreviated to 'G'.

The findings mark the culmination of over 10 years investigation by scientists to show these complex structures in vivo - in living - working from the hypothetical, through computational modelling to synthetic lab experiments and finally the identification in human using fluorescent biomarkers.

The research, published today in Nature Chemistry and funded by Cancer Research UK, goes on to show clear links between concentrations of four-stranded quadruplexes and the process of DNA replication, which is pivotal to cell division and production.

By targeting quadruplexes with synthetic molecules that trap and contain these DNA structures - preventing cells from replicating their DNA and consequently blocking cell division - scientists believe it may be possible to halt the runaway cell proliferation at the root of cancer.

"We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting," said Professor Shankar Balasubramanian from the University of Cambridge's Department of Chemistry and Cambridge Research Institute, whose group produced the research.

"The research indicates that quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells. For us, it strongly supports a new paradigm to be investigated - using these four-stranded structures as targets for personalised treatments in the future."

Physical studies over the last couple of decades had shown that quadruplex DNA can form in vitro - in the 'test tube', but the structure was considered to be a curiosity rather than a feature found in nature. The researchers now know for the first time that they actually form in the DNA of human cells.

"This research further highlights the potential for exploiting these unusual DNA structures to beat cancer – the next part of this pipeline is to figure out how to target them in tumour cells," said Dr Julie Sharp, senior science information manager at Cancer Research UK.

"It's been sixty years since its structure was solved but work like this shows us that the story of DNA continues to twist and turn."

The study published today was led by Giulia Biffi, a researcher in Balasubramaninan's lab at the Cambridge Research Institute.

By building on previous research, Biffi was able to generate antibody proteins that detect and bind to areas in a rich in quadruplex-structured DNA, proving their existence in living human cells.

Using fluorescence to mark the antibodies, the researchers could then identify 'hot spots' for the occurrence of four-stranded DNA - both where in the genome and, critically, at what stage of cell division.

While quadruplex DNA is found fairly consistently throughout the genome of human cells and their division cycles, a marked increase was shown when the fluorescent staining grew more intense during the 's-phase' - the point in a cell cycle where DNA replicates before the cell divides.

Cancers are usually driven by genes called oncogenes that have mutated to increase DNA replication - causing to spiral out of control, and leading to tumour growth.

The increased DNA replication rate in oncogenes leads to an intensity in the quadruplex structures. This means that potentially damaging cellular activity can be targeted with synthetic molecules or other forms of treatments.

"We have found that by trapping the quadruplex DNA with we can sequester and stabilise them, providing important insights into how we might grind to a halt," said Balasubramanian.

"There is a lot we don't know yet. One thought is that these quadruplex structures might be a bit of a nuisance during DNA replication - like knots or tangles that form.

"Did they evolve for a function? It's a philosophical question as to whether they are there by design or not - but they exist and nature has to deal with them. Maybe by targeting them we are contributing to the disruption they cause."

The study showed that if an inhibitor is used to block DNA replication, quadruplex levels go down - proving the idea that DNA is dynamic, with structures constantly being formed and unformed.

The researchers also previously found that an overactive gene with higher levels of Quadruplex DNA is more vulnerable to external interference.

"The data supports the idea that certain cancer genes can be usefully interfered with by small molecules designed to bind specific DNA sequences," said Balasubramanian.

"Many current cancer treatments attack DNA, but it's not clear what the rules are. We don't even know where in the genome some of them react - it can be a scattergun approach.

"The possibility that particular cancer cells harbouring genes with these motifs can now be targeted, and appear to be more vulnerable to interference than normal cells, is a thrilling prospect.

"The 'quadruple helix' may well be the key to new ways of selectively inhibiting the proliferation of cancer cells. The confirmation of its existence in human cells is a real landmark."

Explore further: Structure of sodium channels different than previously believed

Related Stories

Novel technique reveals dynamics of telomere DNA structure

Jan 17, 2013

Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. In a new study, scientists at UC Santa Cruz used a novel technique to reveal structural ...

Scientists identify molecular basis for DNA breakage

Jul 19, 2011

Scientists from the Hebrew University have identified the molecular basis for DNA breakage, a hallmark of cancer cells. The findings of this research have just been published in the journal Molecular Cell.

Researchers demonstrate why DNA breaks down in cancer cells

May 03, 2011

Damage to normal DNA is a hallmark of cancer cells. Although it had previously been known that damage to normal cells is caused by stress to their DNA replication when cancerous cells invade, the molecular basis for this ...

Recommended for you

Breakthrough points to new drugs from nature

Apr 16, 2014

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

World's first successful visualisation of key coenzyme

Apr 16, 2014

Japanese researchers have successfully developed the world's first imaging method for visualising the behaviour of nicotine-adenine dinucleotide derivative (NAD(P)H), a key coenzyme, inside cells. This feat ...

User comments : 18

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
1.7 / 5 (12) Jan 20, 2013
Whenever something of great significance is published, since Scientists of Various interests come across it...Some of them may immediately get good ideas as a flash.... but not have time to provide their valuable comments. So, Preferably the following should happen:

A copy button should be available on pressing of which a blank Notepad page should open up on user's PC and also article's title & URL link should be automatically sent to that blank Notepad page.

Later on when they have time they can press a Bookmark Button for a GENERIC WEB PAGE on their PC
and
can submit both the title & URL where it was read & opinions/comments of them after Pressing a Sent button available on that GENERIC WEB PAGE.

This will avoid missing the comments & still get credit.
nkalanaga
5 / 5 (5) Jan 20, 2013
Or you can do it manually by copying the URL and title from your browser to Notepad. I've done that a lot of times. Another option is to simply bookmark the page in your browser.
mrcoldheart
5 / 5 (1) Jan 20, 2013
In short, inhibiting cancer by targeting it's quadruple helix footprint within our DNA.

I just want to know how long before this becomes possible?
seb
5 / 5 (2) Jan 20, 2013

A copy button should be available on pressing of which a blank Notepad page should open up on user's PC and also article's title & URL link should be automatically sent to that blank Notepad page.


This would be a gross violation of the security protocols protecting your computer against internet based attacks of various kinds.

betterexists
1 / 5 (6) Jan 20, 2013

This would be a gross violation of the security protocols protecting your computer against internet based attacks of various kinds.



Obviously Microsoft should take care of that GENERIC WEB PAGE, Bookmark button and Procedural aspects of it for Windows PCs and others for rest of their operating systems.

Bottom line is Automation of the Entire Operation.

It is extra business for Microsoft etc and new, improved system for us the Readers.
Arcbird
1 / 5 (1) Jan 20, 2013
This article doesn't make the finding justice. I bet you anything they will find a reason just as "rational" as this when they find 6, 8 and 12 helix dna as well.
betterexists
1 / 5 (4) Jan 20, 2013
And also Wide Publicity for the Websites that appear on that GENERIC WEB PAGE.
typicalguy
not rated yet Jan 20, 2013
I guess this means I'm twice these I thought I was!
nickc
3.7 / 5 (3) Jan 20, 2013
Check out "Rosalind Franklin" to see who did a lot of the initial 1950's X-Ray diff work on DNA's structure, and never gets any credit. For shame.
Tausch
1 / 5 (2) Jan 20, 2013
For those who thought they were the sum of their genes...
For those who thought they were more the sum of their...

And so on...
Tausch
1 / 5 (2) Jan 20, 2013
[than] the
(typo correction for the second sentence)
Haste makes error.
GraemeMcRae
not rated yet Jan 20, 2013
Dear betterexists,
Install Chrome, and then take a look through the Chrome extensions. Maybe the thing you're looking for already exists.
TheGhostofOtto1923
1.5 / 5 (8) Jan 20, 2013
A copy button should be available on pressing of which a blank Notepad page should open up on user's PC and also article's title & URL link should be automatically sent to that blank Notepad page.

Later on when they have time they can press a Bookmark Button for a GENERIC WEB PAGE on their PC
and
can submit both the title & URL where it was read & opinions/comments of them after Pressing a Sent button available on that GENERIC WEB PAGE.
Is this what you're talking about?

http://www.nytime...tml?_r=0
TylerH
1 / 5 (1) Jan 20, 2013
Whenever something of great significance is published, since Scientists of Various interests come across it...Some of them may immediately get good ideas as a flash.... but not have time to provide their valuable comments. So, Preferably the following should happen:

A copy button should be available on pressing of which a blank Notepad page should open up on user's PC and also article's title & URL link should be automatically sent to that blank Notepad page.

Later on when they have time they can press a Bookmark Button for a GENERIC WEB PAGE on their PC
and
can submit both the title & URL where it was read & opinions/comments of them after Pressing a Sent button available on that GENERIC WEB PAGE.

This will avoid missing the comments & still get credit.

Or you could just not be lazy and bookmark the site within your browser yourself...
rytucker
5 / 5 (2) Jan 21, 2013
This quadruple helix stuff is pretty unimpressive compared to the comments about browser bookmarks....
frajo
5 / 5 (1) Jan 21, 2013
In short, inhibiting cancer by targeting its quadruple helix footprint within our DNA.
I just want to know how long before this becomes possible?
We don't even know whether it will be useful or harmful:
"...Maybe by targeting them we are contributing to the disruption they cause."

betterexists
1 / 5 (3) Jan 21, 2013
A copy button should be available on pressing of which a blank Notepad page should open up on user's PC and also article's title & URL link should be automatically sent to that blank Notepad page.

Later on when they have time they can press a Bookmark Button for a GENERIC WEB PAGE on their PC
and
can submit both the title & URL where it was read & opinions/comments of them after Pressing a Sent button available on that GENERIC WEB PAGE.
Is this what you're talking about?

http://www.nytime...tml?_r=0

sounds good. Here is the link from that nytimes article.
http://www.instapaper.com/
Isaacsname
1 / 5 (1) Jan 21, 2013
New-agers should have a field day with this.

David Wilcock will tell us it's part of the ascension that kicks off the " acockalypse ".

More news stories

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...