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Four-Stranded DNA Makes Human Debut

Contrary to biological dogma, it appears human DNA can sometimes form a quadruple helix.

By Breanna Draxler|Monday, January 27, 2014
RELATED TAGS: GENETICS
quad-helix
quad-helix

This top view of a G-quadruplex shows its structure in the DNA of a human telomere, where they frequently form.

Thomas Splettstoesser/Wikimedia Commons

In describing the two-stranded structure of DNA, Cambridge University biologists James Watson and Francis Crick gave us the image of a twisting ladder they called a double helix. The rungs were connected by pairs of chemical bases called nucleotides: Adenine (A) paired with thymine (T), and cytosine (C) with guanine (G). 

Now, 60 years later, researchers from the same institution have found a quadruple helix — previously described only in microorganisms — in human cells. In place of rungs, the twisting, four-sided tower has platforms with a guanine nucleotide on each of four corners, hence the name G-quadruplex.

Chemist Shankar Balasubramanian and colleagues found the structures by engineering a special, fluorescent antibody that binds specifically to the four-stranded form. Initial results, published in January, trace the structures to cellular regions associated with explosive growth: telomeres, the protective caps of chromosomes implicated in aging and longevity, and cancer-causing genes. 

G-quadruplexes may be linked to cancer, speculates molecular biologist David Tannahill, a member of the Cambridge team. If his suspicion bears out, then deploying these antibodies, which halt the replication of the quads, could present a means of treating malignant tumors. 

quad-helix-lit
quad-helix-lit

The antibody used in the study, called BG4, binds with quadruple helices and glows red. The glowing structures are visible here in the nucleus of a human bone cancer cell (left) and on the telomeres at the ends of chromosomes in cervical cancer cells (right).

Jean-Paul Rodriguez and Giulia Biffi/Cancer Research UK Cambridge Institute

What’s a G-Quadruplex?

The G-quadruplex is like a three-dimensional tower with multiple floors. Each floor, called a tetrad, has a guanine (G) base on all four corners. These G’s are held together with hydrogen bonds. A single strand of DNA can fold onto itself to form a G-quadruplex, or guanines from multiple strands can bond to form the four-stranded structure.

[This article originally appeared in print as "Four-Stranded DNA Makes Human Debut."] 

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