(PHILADELPHIA)Researchers at The Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.
Researchers have attempted for more than a decade to find drugs that shut down telomerasewidely considered the No. 1 target for the development of new cancer treatmentsbut have been hampered in large part by a lack of knowledge of the enzyme's structure.
The findings, published online August 31 in Nature, should help researchers in their efforts to design effective telomerase inhibitors, says Emmanuel Skordalakes, Ph.D., assistant professor in Wistar's Gene Expression and Regulation Program, who led the study.
"Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells," Skordalakes says. "That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule's critical protein component. It reveals surprising details, at the atomic level, of the enzyme's configuration and how it works to replicate the ends of chromosomesa process critical to both tumor development and the aging process.
In humans, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during cell division.
When telomerase is dormant, telomeres shorten each time a cell divides, leading eventually to genetic instability and cell death. By preserving chromosomes' integrity, telomerase allows cells to continue living and dividing. The enzyme is a
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The Wistar Institute