A research group led by Professor Shankar Balasubramanian (Natural Sciences 1985) has shown for the first time that DNA exists as a quadruple helix in human cells.
Pictured: Professor Balasubramanian (photograph by John Holman).
The quadruple helix has been known for several years to be possible: it has been observed in single-celled ciliates, and has even observed and studied in vitro in human DNA. But this is the first time that the structure has been identified in vivo in human cells. The discovery - published this week in Nature Chemistry, sixty years after Watson and Crick announced (to drinkers in The Eagle) their famous discovery of the iconic double helix – could have profound implications for the treatment of cancer.
Because the quadruple helix motif forms in regions rich in guanine (one of the four bases that comprise DNA molecules), it is known as the G-quadruplex. Professor Balasubramanian’s group created fluorescent antibodies which can bind to G-quadruplexes in the DNA of a target cell and which glow under a specific wavelength of light. By monitoring the fluorescence under a microscope, the group found a peak in the number of G-quadruplexes during the S-phase of the cell cycle - the phase in which DNA is replicated in preparation for cell division.
Pictured, left: a visualization of human cancer cell nuclei. The red dots are foci of the antibody BG4, indicating the presence of G-quadruplex structures.
The research also found that G-quadruplexes appear in greater numbers in cells that are dividing unusually rapidly. As the spread of cancer is linked to abnormal, rapid cell division, the team has concluded that G-quadruplexes are a potential target for cancer treatment. The use of therapeutic molecules that bind to G-quadruplex regions could specifically prevent the proliferation of cancer cells. Balasubramanian said: "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. 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.”
Professor Shankar Balasubramanian read Natural Sciences at Fitzwilliam from 1985-88, and stayed to read for his PhD in Enzyme Chemistry. He is Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge. Past work includes the invention of the ‘Solexa’ DNA Sequencing technique, which revolutionised the field of genome sequencing.