Fighting a Deadly Enzyme

Scientists are drawing closer to understanding the structure of the enzyme telomerase, which plays a significant role in aging and most cancers.

Investigators from UCLA and UC Berkeley have produced images of telomerase in much higher resolution than ever before, giving them major new insights about the enzyme. Their findings, published by the journalScience, could ultimately lead to new directions for treating cancer and preventing premature aging.

“Many details we could only guess at before, we can now see unambiguously, and we now have an understanding of where the different components of telomerase interact,” said Juli Feigon, a professor of chemistry and biochemistry in the UCLA College and a senior author of the study. “If telomerase were a cat, before we could see its general outline and the location of the limbs, but now we can see the eyes, the whiskers, the tail and the toes.”

According to a news release from UCLA, the research brought together experts in structural biology, biochemistry and biophysics, and a wide range of cutting-edge research techniques.

The primary job of telomerase is to maintain the DNA in telomeres, the structures at the ends of our chromosomes that act like the plastic tips at the ends of shoelaces. When telomerase isn’t active, each time our cells divide, the telomeres get shorter. When that happens, the telomeres eventually become so short that the cells stop dividing or die.

On the other hand, cells with abnormally active telomerase can constantly rebuild their protective chromosomal caps and become immortal. Making cells immortal might sound like a promising prospect, but it actually is harmful because DNA errors accumulate over time, which damages cells, said Feigon.

Telomerase is particularly active in cancer cells, which helps make them immortal and enables cancer to grow and spread. Scientists believe that controlling the length of telomeres in cancer cells could be a way to prevent them from multiplying.

“Our research may make those things achievable, even though they were not our goals,” Feigon said. “You never know where basic research will go. When telomerase and telomeres were discovered, no one had any idea what the impact of that research would be. The question was, ‘How are the ends of our chromosomes maintained?’ We knew there had to be some activity in the cell that does that.”

“There is so much potential for treating disease if we understand deeply how telomerase works,” Feigon said.

Among the technologies the researchers used to produce the groundbreaking images were UCLA’s cryoelectron microscopes, which are housed in the laboratory of Z. Hong Zhou, director of the Electron Imaging Center for Nanomachines at the California NanoSystems Institute at UCLA and a co-author of the paper. The researchers also used nuclear magnetic resonance spectroscopy, X-ray crystallography, mass spectrometry and biochemical methods.