A new technique and “optical tweezers” have let researchers observe telomerase activity at a single-molecule level with unprecedented precision.
The new work expands our understanding of the vital enzyme and is a step toward better cancer treatments.
Stem cells involved in replenishing human tissues and blood depend on telomerase to continue working throughout our lives. When telomerase malfunctions, it can lead to both cancer and premature aging conditions. Roughly 90% of cancer cells require inappropriate telomerase activity to survive.
Optical tweezers use powerful lasers to create small forces capable of pushing, pulling, and holding microscopic objects, like individual strands of DNA or a telomerase enzyme.
“By watching the telomerase work in real time, we can learn how it functions in full detail.”
“Our optical tweezer method lets us take the little machines out of the cell, gently hold onto them, and watch them go,” says coauthor Matthew Comstock, assistant professor in the physics and astronomy department and chair of experimental physics at Michigan State University. “By watching the telomerase work in real time, we can learn how it functions in full detail.”
As stem cells divide over time, the chromosomes gradually decrease in length. A telomere—a disposable buffer of repeating DNA sequences—caps the end of each chromosome.
The telomerase enzyme attaches to the telomere buffer and replaces most of the sequences lost during replication. It was thought that telomerase made progressive extensions in a single step, but scientists could only theorize as to how it stayed in contact and aligned with the right sequence.
What the researchers found was essentially a safety harness anchored to the chromosome in a seemingly specific location.
“In an ideal world we could inhibit telomerase in cancer cells without affecting stem cells,” says coauthor Jens Schmidt, assistant professor in the obstetrics, gynecology, and reproductive biology department.
“This anchor site is a potential drug target. If we or someone else finds a molecule that interferes with the telomerase anchor site, telomerase would fall off the chromosome end faster, stopping its activity.”
The team hopes their method and discovery will help others in their research.
“It is very important that we also are showing other teams with optical tweezer instruments like ours how to do these experiments,” Comstock says.
For Schmidt and Comstock, this discovery is the realization of a long-term goal—it sets the stage for a wide range of new research opportunities. And most importantly, it brings safer and more effective cancer treatments one step closer.
The study appears in Nature Chemical Biology.
Source: Michigan State University
