How Do Cancer Cells Protect Their Telomeres?

Skin cancer cells. Credit: National Institutes of Health

15% of cancers use a process called ALT to extend their telomeres, and research has revealed that this involves a 'hijacking' of DNA repair mechanisms

To sustain their incredible growth cancer cells must protect their telomeres from shortening and the majority of them use the enzyme telomerase to do this. This is a relatively well understood process, but it's still unclear how the more insidious 15% of cancers use a mechanism called Alternative Lengthening of Telomeres (ALT) to do the same job. ALT cancers are particularly aggressive and difficult to treat, and understanding the ALT process could open the door to new drug development and even alternative methods of telomere extension. 

"Identifying the parts that the cancer cell tweaks to reset the countdown timer could provide targets for developing new cancer drugs or making existing ones more effective"

A link to DNA repair

A team from University of Pittsburgh Cancer Institute has discovered 139 proteins associated uniquely with ALT activity. This was achieved using a new technique called proximity dependent biotinylation (BioID). This highlights proteins nearby to a specific target - in this case telomeres. Of these 139 proteins, the researchers were surprised to discover DNA polymerase, an enzyme that plays a critical role in building new strands of DNA.  DNA polymerase is known to be activated in cells exposed to UV light, but this is the first time it has been tied to telomere extension. Further study of the remaining proteins will reveal further insights into these rare cancers, which could provide a new platform of attack. 

"We expected to see DNA repair proteins, but seeing Polη was really unexpected as it was known to be activated only in cells that were damaged by UV light, which we did not use in our experiments. Its role in the ALT pathway is completely independent of how we think of it normally"

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