Study reveals key structure in telomerase enzyme, a target for cancer drugs

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Fishermangents
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Study reveals key structure in telomerase enzyme, a target for cancer drugs

Post by Fishermangents » Wed Apr 06, 2016 11:06 pm

Science Daily, 5 October 2015

Over-activation of telomerase in 90 percent of malignant tumors has made the unusual enzyme a prime target for drug development efforts

Date: October 5, 2015
Source: University of California - Santa Cruz
Summary: Researchers have determined the structure of a key part of the enzyme telomerase, which is active in most cancers and enables cancer cells to proliferate indefinitely. The new findings reveal how the enzyme carries out a crucial function involved in protecting the ends of chromosomes.

Researchers at UC Santa Cruz have determined the structure of a key part of the enzyme telomerase, which is active in most cancers and enables cancer cells to proliferate indefinitely. The new findings, published October 5 in Nature Structural & Molecular Biology, reveal how the enzyme carries out a crucial function involved in protecting the ends of chromosomes. Repetitive DNA sequences at the ends of chromosomes, called telomeres, serve as protective caps (often compared to the plastic tips on shoelaces). As cells divide, their telomeres get progressively shorter, until eventually the cells stop dividing. The telomerase enzyme lengthens telomeres by adding more of the repetitive DNA sequence. It is active in cells that need to keep dividing indefinitely, such as stem cells, and in about 90 percent of malignant tumors.

"Since the discovery of telomerase and its over-activation in cancers, people have recognized the huge therapeutic potential for anticancer drugs that target telomerase. But there still is no such drug in the clinic, and part of the reason is our lack of understanding of the detailed structure of the enzyme," said Michael Stone, associate professor of chemistry and biochemistry at UC Santa Cruz and senior author of the paper.

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"Our model is consistent with the findings of other studies of telomerase and directly reveals the functional mechanism involved," Stone said. "What makes this interesting for rational drug design is that template boundary definition is a very specific feature of telomerase. Our cells are full of other kinds of polymerase enzymes, so it's important to design a drug that targets only telomerase."

link: https://www.sciencedaily.com/releases/2 ... 120917.htm

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