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Archive - Jan 17, 2013

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Novel Technique Reveals Dynamics of Telomere DNA Structure

Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. In a new study, scientists at the University of California-Santa Cruz used a novel technique to reveal structural and mechanical properties of telomeres that could help guide the development of new anti-cancer drugs. Telomeres are long, repetitive DNA sequences at the ends of chromosomes that serve a protective function analogous to that of the plastic tips on shoelaces. As cells divide, their telomeres get progressively shorter, until eventually the cells stop dividing. Telomeres can grow longer, however, through the action of an enzyme called telomerase, which is especially active in cells that need to keep dividing indefinitely, such as stem cells. Researchers have also found that most tumor cells show high telomerase activity. Dr. Michael Stone, an assistant professor of chemistry and biochemistry at UC-Santa Cruz, said his lab is particularly interested in the folding and unfolding of a DNA structure at the tail end of the telomere, known as a G-quadruplex, because it plays a key role in regulating telomerase activity. "Most cancer cells use telomerase as one mechanism to maintain uncontrolled growth, so it is an important target for anti-cancer therapeutics," Dr. Stone said. "The G-quadruplex structures of telomere DNA inhibit the function of the telomerase enzyme, so we wanted to understand the mechanical stability of this structure." Xi Long, a graduate student in Dr. Stone's lab, led the project, which involved integrating two techniques to manipulate and monitor single DNA molecules during the unfolding of the G-quadruplex structure.

Potential New Treatment for Gastrointestinal Cancers Discovered

Researchers have identified a complex of proteins that promotes the growth of some types of colon and gastric cancers, and shown that medications that block the function of this complex have the potential to be developed into a new treatment for these diseases. The complex of proteins, known as mTorc1 (mammalian target of rapamycin complex 1), has previously been implicated in the development of some other cancers, but this is the first time it has been shown to promote the growth of colon and gastric cancers that are associated with inflammation. Dr Stefan Thiem and Associate Professor Matthias Ernst from the Walter and Eliza Hall Institute’s Cell Signalling and Cell Death division made the discovery with colleagues while at the Melbourne-Parkville Branch of the Ludwig Institute for Cancer Research. Associate Professor Ernst is a Ludwig Institute Member. Their findings were published online on January 16, 2013 in the Journal of Clinical Investigation. Cancers of the digestive system are a significant cause of death in Australia. Colon (or bowel) cancer causes more than 4,000 deaths annually – more than any other cancer except lung cancer – while more than 1,000 Australians die from gastric (or stomach) cancer each year. Associate Professor Ernst said many types of colon and gastric cancer are associated with chronic inflammation. “We have previously shown that the immune system’s inflammatory response can promote the growth of tumors,” he said.