Before cells divide, they have to unwind their chromosomes, copy of all of their DNA, and then wrap the DNA backup into chromosomes. When this process happens, cells often lose a little bit of DNA from the tips of their chromosomes. An enzyme, called telomerase, can help repair chromosomes by adding that DNA back onto the ends. Scientists are interested in telomerase because inhibiting it could help prevent the growth of rapidly dividing cells, like those found in cancer tumors.
While telomerase was discovered back in 1984, it has been difficult for researchers to design drugs that interact with it because the enzyme’s structure was not well understood. Traditional methods of imaging enzymes, like forming a solid crystal of telomerase and then inferring the enzyme’s structure based on how x-rays bounced off, had been performed on telomerase, but were not able to give a picture with a high resolution.
Kelly Nguyen and her team at the University of California, Berkley have taken a step forward in understanding telomerase. After carefully growing cells and collecting the enzyme, the team imaged their samples using a process called cryo-electron microscopy. Cryo-electron microscopy is a novel imaging technique that won the Nobel Prize in chemistry in 2017. This technique rapidly freezes a sample before imaging, allowing scientists to observe a snapshot of their specimen in action, with a resolution of about 0.8 nm.
The team’s image reveals that telomerase has two lobes. One lobe is made of proteins and is responsible for making sure the protein moves where it is needed in the cell. The second lobe contains proteins that actually repair the lost DNA at the tips of chromosomes. The two lobes are held together by a little bit of RNA, a molecule similar to DNA.
Our expert, Mitch Mcvey, a biology professor at Tufts, explains that the work by Nguyen and her team makes three major advances. The technique could help scientists understand the structures of other related proteins. Additionally, understanding the protein structure of telomerase could help corroborate behavior other scientists have observed. The work could also provide a route to studying human illnesses influenced by too much or too little telomerase, including certain types of premature aging and cancer.
Managing Correspondent: Emily Kerr
Acknowledgements: Many thanks to Mitch McVey, a professor at Tufts for his input on this article.
Scientific Article: Cryo-EM structure of substrate-bound human telomerase holoenzyme