New research just published in high impact scientific publication, Cell Reports resolves some long-standing confusion in the cancer research field and also opens up the possibility for new combined therapies for treatment of 85% of all cancers with fewer side effects.
The study reveals that two unexpected factors are important for this process in cancer cells. These factors are, ATM and ATR, key signalling molecules inside cells that respond to DNA damage, like that which occurs during cancer development through exposure to chemicals or UV light. These molecules are involved in telomerase action in yeast cells, but were thought not to be involved in human cancer cells.
Led by Associate Professor Tracy Bryan, lead authors CMRI’s final year PhD student Adrian Tong and Cell Biology researcher Joshua Lewis Stern, collaboratively worked alongside colleagues at The Rockefeller University in New York and McMaster University in Ontario Canada to find that when either of these molecules (ATM or ATR) are missing, the telomere clock cannot be reset. Specifically, telomerase needs ATM and ATR in order to assemble and in order to reach telomeres.
This means that new cancer treatments under development, some aimed at impairing telomerase function and others aimed at ATM, could be used together to increase their effectiveness against most types of cancer.
The details of how ATM and ATR can control telomerase are described in the paper, ‘ATM and ATR signalling regulate the recruitment of human telomerase to telomeres’ , as well as further evidence that specific types of DNA damage can trigger telomerase action. In effect, cancer cells are stacking the odds in their favour by exploiting the way that normal cells protect themselves against DNA damage, and using it to turn themselves “immortal”.
Because ATM is required for recruitment of telomerase to telomeres in human cell lines, this also explains the long-standing observation of short telomeres in the ATM-deficient cells of ataxia telangiectasia (AT) patients, who have impaired brain function, signs of premature aging, as well as increased risk of certain types of cancers.
This research has been published in the journal Cell Reports, and is accompanied by an article from the lab of Professor Carol Greider at Johns Hopkins University, showing similar results with a different and complementary method. The abstract of the published article is now available online here.