Molecular machines stop cancer’s clock

Scientists at WA’s Harry Perkins Institute of Medical Research have developed a way to wrap artificial proteins around the ends of chromosomes to effectively block the uncontrolled growth that occurs with most cancers.

Oliver RackhamHead of the laboratory for Synthetic Biology and Drug Discovery, Associate Professor Oliver Rackham, says cancer cells grow uncontrollably whereas normal cells limit their growth.

“A normal cell grows for just the right amount of time that is required for us to develop and maintain our bodies. 

“They control their growth with a molecular counting mechanism that tells the cell how old it is. This occurs on the ends of our chromosomes which have little caps on them. Each time the cell divides a little bit at the cap of the chromosome disappears. Once the caps shrink to a certain length the cell knows that it has divided too many times and it will then stop growing or die.

“However, cancer cells subvert the counting mechanism that shrinks the ends of our chromosomes so cancer cells keep replicating indefinitely.

“The way cancer cells avoid this control mechanism is by producing an enzyme called telomerase which we need when we are babies and growing very fast but which we stop producing when we stop rapidly growing,” he said.

Professor Rackham says about 90% of cancer cells have the telomerase enzyme, when they shouldn’t.

The enzyme extends the ends of the single strands of the DNA, or the caps in cancer cells, which effectively sends the message ‘we’re going to live forever’. So the chromosome thinks it’s a brand new chromosome. 

Professor Rackham’s team at the Perkins has engineered proteins that effectively clamp tightly around the end of the single stranded DNA in the chromosome.

“These proteins lock down the DNA so telomerase can’t touch it.”

“Our laboratory designed proteins that, for the first time, can actually recognise the single stranded DNA and bind it. We can basically program these proteins to target them.

“Previously scientists haven’t been able to target the single stranded DNA.

“The beauty of this new technology is that we have developed proteins that can actually recognise the DNA and bind to it.”

Professor Rackham, says the work was a collaboration with researchers at the Max Planck Institute for Biology of Ageing in Cologne, Germany and the Children's Medical Research Institute in Sydney. 

It has been reviewed by leading international scientists and was published on 7 June in the prestigious international journal Nature Communications.

Professor Rackham is a Cancer Council WA Research Fellow. His research is supported by the Australian Research Council.

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