Navigation Links
'Quadruple helix' DNA discovered in human cells
Date:1/20/2013

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 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."


'/>"/>

Contact: Fred Lewsey
fred.lewsey@admin.cam.ac.uk
44-078-857-98680
University of Cambridge
Source:Eurekalert

Related biology news :

1. First description of a triple DNA helix in a vacuum
2. Doubling the information from the double helix
3. Unexpected crustacean diversity discovered in northern freshwater ecosystems
4. University of Alberta led research may have discovered how memories are encoded in our brains
5. Newly discovered foot points to a new kid on the hominin block
6. New immune defense enzyme discovered
7. New genetic mechanism of immune deficiency discovered
8. Housekeeping mechanism for brain stem cells discovered
9. Scientists have discovered genes that increase the risk of osteoporosis and fractures
10. New form of intellectual disability discovered
11. 24 new species of lizards discovered on Caribbean islands are close to extinction
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... 5, 2017  The Allen Institute for Cell Science ... a one-of-a-kind portal and dynamic digital window into the ... the first application of deep learning to create predictive ... lines and a growing suite of powerful tools. The ... and future publicly available resources created and shared by ...
(Date:4/3/2017)... 3, 2017  Data captured by IsoCode, ... detected a statistically significant association between the ... treatment and objective response of cancer patients ... predict whether cancer patients will respond to ... well as to improve both pre-infusion potency testing ...
(Date:3/29/2017)... 29, 2017  higi, the health IT company that ... North America , today announced a Series B ... of EveryMove. The new investment and acquisition accelerates higi,s ... to transform population health activities through the collection and ... higi collects and secures data today on behalf ...
Breaking Biology News(10 mins):
(Date:4/20/2017)... Dutch philosopher Koert van Mensvoort - founder of the Next Nature Network ... - has written a ,Letter to Humanity, in support of International ... a slave and victim to its own technology, but to employ technology to ... ... – founder of the Next Nature Network and Fellow of ‘Next Nature’ at ...
(Date:4/19/2017)... (PRWEB) , ... April 18, 2017 , ... A number ... advances. This webinar, which is part of the Protein and Cell Analysis Education ... and outline where this technology fits in current and future applications. , Many ...
(Date:4/19/2017)... ... April 19, 2017 , ... ThermaGenix, the PCR Improvement Company, ... to several other early achievements at ThermaGenix, including the business formation and licensing ... ThermaGenix will use proceeds from the Series A-1 round to:, ...
(Date:4/19/2017)... Calif. , April 19, 2017  As ... Drug Abuse and Heroin Summit ,  Proove® Biosciences, ... study analyzing genetics, environmental, and lifestyle factors to ... from the University of Southern California (USC), the ... , and Proove publish results showing that Proove ...
Breaking Biology Technology: