DNA trick may be clue to cancer cells' eternal life

Cancer Research UK

Cancer Research UK scientists have uncovered a new strategy that could be used by cancer cells to side step the body’s normal safety checks and become immortal – a key step for a cancer cell – according to a study published in Nature today (Thursday)*.

The strategy involves cells topping up their biological clock by making copies of spare DNA found elsewhere in the genome to replace the protective caps – called telomeres – usually found at the ends of chromosomes.

In most cells of the body, telomeres shorten each time the cell divides. Once a critical length is reached, it triggers the cell to die - acting like an in-built timer to ensure that the cell can’t live past its pre-programmed expiry date.

But in around 85 per cent of cases, cancer cells manage to get around this safety check by reactivating telomerase – an enzyme that can rebuild the telomeres by creating new DNA repeats.

This study in yeast cells highlights one possible way that the remaining 10-15 per cent of cancer cells lacking telomerase could get around the problem of their biological clocks running out.

The discovery adds to our understanding of how cancer cells could become immortal, and may unlock new avenues of research for the development of cancer treatments.

Lead author Dr Julie Cooper, based at Cancer Research UK’s London Research Institute, said: “Our research reveals an alternative means by which yeast cells can protect their chromosome ends.

“Until now fruit flies were the only living things known to be able to survive and maintain linear chromosomes without ‘classical’ telomeres. But discovering a similar system in yeast, which are very far from fruit flies on the evolutionary scale, suggests it could be much more universal than previously thought and could even play a role in some human cancers.”

“Research to find out whether human cells can also use this alternative system to protect their chromosomes and what role, if any, it could play in tumour growth, could reveal interesting new avenues for interrupting the ‘immortalisation’ that cancer cells undergo.”

To make their discovery, the researchers deleted the gene that codes for telomerase in yeast cells. Usually this would cause the telomeres to be lost and the exposed chromosome ends to fuse together, making circular chromosomes. But in a small number of yeast cells the chromosomes didn’t fuse, suggesting that these rare survivors had found another strategy for protecting their chromosome ends.

When the researchers studied these more closely they found that, to make up for their lack of telomeres, the surviving cells had hijacked spare DNA sequences from elsewhere in the genome. They had then made copies of these and transferred them to the chromosome ends where they were acting as a protective buffer.

Dr Helen George, head of science information at Cancer Research UK, said: “Our researchers have discovered a new tactic that could be used by cancer cells to cheat death.

“It raises the possibility that drugs could be developed to restore their natural life span and halt the growth and spread of cancers.”

ENDS

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References

  • Jain, D., Hebden, A., Nakamura, T., Miller, K., & Cooper, J. (2010). HAATI survivors replace canonical telomeres with blocks of generic heterochromatin Nature, 467 (7312), 223-227 DOI: 10.1038/nature09374