Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Four-Stranded ‘Quadruple Helix’ DNA Structure Proven to Exist in Human Cells

Published: Monday, January 21, 2013
Last Updated: Monday, January 21, 2013
Bookmark and Share
Discovery opens up possibilities for a new generation of targeted therapies for cancer.

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 human cells – working from the hypothetical, through computational modelling to synthetic lab experiments and finally the identification in human cancer cells 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 human genome 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 cell proliferation 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 synthetic molecules we can sequester and stabilise them, providing important insights into how we might grind cell division 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’ DNA structure 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.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Ancient Genome from Africa Sequenced for the First Time
DNA from 4,500-year-old Ethiopian skull reveals a huge migratory wave of West Eurasians into the Horn of Africa around 3,000 years ago had a genetic impact on modern populations right across the African continent.
Monday, October 19, 2015
Greater Understanding Of Polycystic Ovary Syndrome
A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.
Wednesday, September 30, 2015
Maintaining Healthy DNA Delays Menopause
An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through menopause.
Tuesday, September 29, 2015
New Consortium to Develop and Study Early Stage Drugs
An innovative new Consortium will act as a ‘match-making’ service between pharmaceutical companies and researchers in Cambridge with the aim of developing and studying precision medicines for some of the most globally devastating diseases.
Thursday, July 30, 2015
MRSA Contamination Found in Supermarket Pork
A survey carried out earlier this year has found the first evidence of the ‘superbug’ bacteria Methicillin-Resistant Staphylococcus Aureus (MRSA) in sausages and minced pork obtained from supermarkets in the UK.
Monday, June 22, 2015
Expression of Certain Genes Changes with the Seasons
As the seasons change, so do the expression levels of many human genes, including ones involved in immune function, according to new research.
Thursday, May 14, 2015
Blood Markers Could Help Predict Outcome Of Infant Heart Surgery
New research suggests it may be possible to predict an infant’s progress following surgery for congenital heart disease by analysing a number of important small molecules in the blood.
Friday, May 08, 2015
Poisons, Plants and Palaeolithic Hunters
Dr Valentina Borgia to develop a technique for detecting residues of deadly substances on archaeological objects.
Saturday, April 11, 2015
‘Mini-Lungs’ Grown To Aid The Study Of Cystic Fibrosis
'Mini-lungs’ have been created using stem cells derived from skin cells of patients with cystic fibrosis.
Thursday, March 19, 2015
Gene Discovery Provides Clues To How TB May Evade The Immune System
The largest genetic study of TB susceptibility to date has led to a potentially important new insight into how the pathogen manages to evade the immune system.
Tuesday, March 17, 2015
Human Genome Includes 'Foreign' Genes Not From Our Ancestors
Many animals, including humans, acquired essential ‘foreign’ genes from microorganisms co-habiting their environment in ancient times, according to research published in the open access journal Genome Biology.
Monday, March 16, 2015
Order Matters: Sequence Of Genetic Mutations Determines How Cancer Behaves
The order in which genetic mutations are acquired determines how an individual cancer behaves, according to research from the University of Cambridge, published today in the New England Journal of Medicine.
Thursday, February 12, 2015
Artificially-intelligent Robot Scientist ‘Eve’ Could Boost Search for New Drugs
Eve, an artificially-intelligent ‘robot scientist’ could make drug discovery faster and much cheaper, say researchers writing in the Royal Society journal Interface.
Wednesday, February 04, 2015
Using Genome Sequencing to Track MRSA in Under-resourced Hospitals
Whole genome sequencing of MRSA from a hospital in Asia has demonstrated patterns of transmission in a resource-limited setting, where formal screening procedures are not feasible.
Thursday, December 11, 2014
Amazing Feet Of Science: Researchers Sequence The Centipede Genome
What it lacks in genes, it certainly makes up for in legs: the genome of the humble centipede has been found to have around 15,000 genes – around 7,000 fewer than a human.
Wednesday, November 26, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos