Regulating telomerase activity

The natural ends of chromosomes resemble broken DNA, posing a challenge in distinguishing them from intact strands. However, every cell must differentiate between the two, as the best method to safeguard the healthy end of a chromosome is also the least effective way to mend damaged DNA.

The enzyme telomerase is responsible for maintaining protective telomeres at the natural ends of chromosomes. If telomerase were to seal off a broken strand of DNA with a telomere, it would prevent further repair of that break and delete essential genes. The study published in Science describes how cells avoid such mishaps. These findings show that telomerase can indeed run amok, adding telomeres to damaged DNA, and would do so were it not for the ATR kinase, a key enzyme that responds to DNA damage.

"Telomerase is a good thing because it maintains our telomeres, but it should only be acting at the natural ends of chromosomes. It is very bad if it acts at double-stranded DNA breaks because it can lead to the loss of all genes distal to the break," says Titia de Lange, the Leon Hess professor at Rockefeller. "This detrimental aspect of telomerase is inhibited by the ATR kinase, which, among its many talents, also keeps telomerase away."