On Sept. 23, KurzweilAI noted that scientists at the Salk Institute had discovered an on-and-off “switch” in cells that might allow for increasing telomerase, which rebuilds telomeres at the ends of chromosomes to keep cells dividing and generating. We also noted that cancer cells hijack this process and that the scientists expect that the “off” switch might help keep telomerase activity below this threshold. Now in another studypublished last week in Cell, Roger Greenberg, MD, PhD, associate professor of Cancer Biology in the Perelman School of Medicine at the University of Pennsylvaniaand his colleagues describe their discovery of a second method used by cancer cells to survive, involving a DNA-repair-based mechanism called “alternative lengthening of telomeres” (ALT).
The researchers found that approximately 15 percent of cancers use the ALT process for telomere lengthening, but that some cancer types use ALT up to 40 to 50 percent of the time. The team showed that when a cancer cell’s DNA breaks, the cell triggers DNA repair proteins (like the breast cancer suppressor protein BRCA2*) into action, along with other helper proteins that attach to the damaged stretch of DNA. These proteins stretch out the DNA, allowing it to search for complementary sequences of telomere DNA. “This process of repair triggers the movement and clustering of telomeres like fish being reeled toward an angler,” explains Greenberg. “The broken telomeres use a telomere on a different chromosome — the homologous telomere — as a template for repair.” In cancer cells that use ALT to maintain their telomeres, the team visualized these clusters of telomeres coming together.