Imaging Telomerase, Cancer’s “Immortality Factor”

Telomerase is an essential enzyme that is implicated in both aging and cancer. In a study published today in Molecular Cell, scientists from the Université de Montréal used advanced microscopy techniques to see single molecules of telomerase in living cells.

Chromosomes get shorter and shorter every time they replicate. If nothing is done to correct this, replication eventually stops and the cell goes into a state called senescence—a hallmark of aging. Some organisms have an enzyme called telomerase that adds extra DNA to the ends of chromosomes to prevent this problem, but the level of telomerase goes down with age.

Part of the reason that tumors are immortal is that cancer cells express telomerase, which allows cells to divide indefinitely. This reactivation is among the first steps that direct cells to become cancerous, but the process remains poorly understood. If researchers knew more about it, they could offer hope for some form of therapy to combat it.

Now, an Université de Montréal team led by biochemistry professor Pascal Chartrand, in collaboration with cell biologist Agnel Sfeir at the Skirball Institute in New York, has succeeded in tagging telomerase with several ultrabright fluorescent molecules.

“With this technological breakthrough, we observed that telomerase continuously probes telomeres but becomes engaged at the ends of chromosomes following a two-step binding mode,” says UdeM biochemist Hadrien Laprade, who, with his colleague Emmanuelle Querido, conducted the experimental investigations.

In their study, the scientists also show how mutation of a telomeric regulatory factor results in an unrestrained access of telomerase to the tips of telomeres, an event that promotes tumorigenesis.

“This new technology now provides sufficient details of how a key actor in cancer works at the molecular level, the first step in developing novels therapeutic strategies to thwart its activity,” Chartrand says. “It could take years before we get there, but this is an important first step.”