Quadruple helix DNA discovered in human cells
Previously the quadruple helix had been formed in the laboratory by
intertwining four strands of DNA however it was long believed that they did not
exist in nature. The four-stranded DNA called the G-quadruplexes, are
formed by the interaction of four guanine bases that together make a square,
and appeared in cells that were ready divide. They form in the core of
chromosomes and on telomeres (tips of chromosomes to protect them from damage),
however since cancer cells have defects in telomeres and divide rapidly, this
may be unique to cancer cells.
The study (published
in Nature and New Scientist) was led by Shankar Balasubramanian, at the University
of Cambridge, with the team using antibodies that could only attach to G-quadruplexes to
locate the G-quadruplexes and then using pyridostatin (a molecule trapping the quadruple helices) to stop them from unraveling into ordinary DNA, enabling
researchers to count the number formed at each stage of cell division. They
found that these quadruple helices were most common in the S-phase (during
Interphase) when cells replicate their DNA, before dividing.
Balasubramanian believes that the G-quadruplexes are triggered into
action by chaotic genomic mutations and reorganizations typical of cancerous of
precancerous cells. Using pyridostatin on human breast cancer cells, the team
found that it stopped the cells from replicating and reduced the spread of
cancer cells. The results, therefore, reinforce the possibility that blocking
G-quadruplexes could combat cancers. However, currently the team is hoping to
find out whether quadruple helices exist in healthy cells and whether they play
a role in embryo development, being mistakenly reactivated in cancer cells.
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