Four-stranded DNA structures found to play role in breast cancer


04-08-2020
  Crystal structure of parallel quadruplexes from human telomeric DNA. The DNA strand (blue) circles the bases that stack together in the center around three co-ordinated metal ions (green)  Credit: Thomas Splettstoesser

Four stranded DNA structures – known as G-quadruplexes – have been shown to play a role in certain types of breast cancer for the first time, providing a potential new target for personalised medicine, say scientists at the University of Cambridge.

In 1953, Cambridge researchers Francis Crick and James Watson co-authored a study published in the journal Nature which showed that DNA in our cells has an intertwined, ‘double helix’ structure. Sixty years later, a team led by Professor Sir Shankar Balasubramanian and Professor Steve Jackson, also at Cambridge, found that an unusual four-stranded configuration of DNA can occur across the human genome in living cells.

These structures form in regions of DNA that are rich in one of its building blocks, guanine (G), when a single strand of the double-stranded DNA loops out and doubles back on itself, forming a four-stranded ‘handle’ in the genome. As a result, these structures are called G-quadruplexes.

Professor Balasubramanian and colleagues have previously developed sequencing technologies and approaches capable of detecting G-quadruplexes in DNA and in chromatin (a substance comprised of DNA and proteins). They have previously shown that G-quadruplexes play a role in transcription, a key step in reading the genetic code and creating proteins from DNA. Crucially, their work also showed that G-quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells.

Now, for the first time, the team has discovered where G-quadruplexes form in preserved tumour tissue/biopsies of breast cancer. Details of their study are published in the journal Nature Genetics.

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Image: Crystal structure of parallel quadruplexes from human telomeric DNA. The DNA strand (blue) circles the bases that stack together in the center around three co-ordinated metal ions (green)

Credit: Thomas Splettstoesser

Reproduced courtesy of the University of Cambridge

 

The University of Cambridge is acknowledged as one of the world's leading higher education and research institutions. The University was instrumental in the formation of the Cambridge Network and its Vice- Chancellor, Professor Stephen Toope, is also the President of the Cambridge Network.

University of Cambridge (cam.ac.uk)