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article imageScientists discover DNA with quadruple helix in cancer cells

By JohnThomas Didymus     Jan 21, 2013 in Science
Cambridge - Scientists at Cambridge have discovered DNA with four helices located in human cancer cells. They say "quadruple helix" DNA could lead to new drugs to fight cancer because if unique to cancer cells it could be possible to develop drugs to target them.
The researchers published their findings in a paper titled "Quantitative visualization of DNA G-quadruplex structures in human cells," in the Nature Chemistry journal.
Quadruple helices consist of four intertwined strands rather than two.
According to the authors, it appears that quadruple helix DNA are formed temporarily when cancer cells are preparing to divide.The researchers say future cancer drugs designed to target these quadruple helices could leave healthy cells unharmed.
Shankar Balasubramanian, professor of chemistry at the University of Cambridge, who supervised the research, said the new discovery challenges the common view that the structure of DNA is fully understood, Mother Nature Network reports.
Scientists have been creating the novel guanine-rich ("G-quadruplex") DNA in laboratories for several years, but this is the first time they have been able to observe them in living tissue, specifically in cancer cells.
Balasubramanian told the BBC: "We've come a long way in 10 years, from simple ideas to really seeing some substance in the existence and tractability of targeting these funny structures. I'm hoping now that the pharmaceutical companies will bring this on to their radar and we can perhaps take a more serious look at whether quadruplexes are indeed therapeutically viable ."
Quadruple helix DNA and cancer cells
DNA (deoxyribonucleic acid) is the hereditary material in humans and other organisms. Cancers in human tissues are caused by genes called oncogenes that exhibit a higher than normal replication activity, leading cell division to spiral out of control in the formation of tumors.
The increased replication rate in oncogenes appears associated with the formation of G-quadruplex structures, an observation that leads to the exciting possibility of developing cancer therapies which target them in cells.
How new cancer drugs may work
Scientists are hoping that the new discovery will help in developing new cancer treatments based on the fact that of the four organic bases (A- Adenine; G-Guanine; C-Cytosine; T- Thymine) that form the genetic code, guanine is present in higher-than-normal levels in quadruple helix DNA.
Quadruple helix DNA structures are called "G-quadruplexes" because they are guanine-rich. According to Nature, a G-quadruplex comprises "four guanines from different places along a G-rich strand held together by a special type of hydrogen bonding to form a compact square structure that interrupts the DNA helix."
Mother Nature Network reports that the lead author, Guilia Biffi, a PhD student in Balasubramanian's laboratory, developed antibody proteins with a fluorescent marker that bind tightly and specifically to G-quadruplex structures and not to double-stranded helical DNA. After locating the G-quadruplex structure with the engineered fluorescent marker, they then used a molecule called pyridostatin to "trap" the quadruple helices in place.
The Daily Mail reports Balasubramanian said: "We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting."
The suggestion is that formation of quadruple helices in actively dividing cells may be a critical factor in the development of cancer. The researchers reason that if it is possible use natural of synthetic substances to "trap" quadruple helices in the manner demonstrated in laboratory, a drug could be developed that targets the G-quadruplexes in cancer therapy.
Balasubramanian told the BBC: "I'm hoping now that the pharmaceutical companies will bring this on to their radar and we can perhaps take a more serious look at whether quadruplexes are indeed therapeutically viable targets... The quadruple helix DNA structure may well be the key to new ways of selectively inhibiting the proliferation of cancer cells."
He concluded: "The confirmation of its existence in human cells is a real landmark."
More about Dna, quadruple helix, Cancer cells
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