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Protecting the Chromosome

Much like the plastic caps at the tips of shoelaces that keep them from unraveling, telomeres cover the ends of our chromosomes to protect the DNA within them. Every time a cell divides, however, the telomeres get shorter, and, after approximately 50 cell divisions, the telomeres reach a critically short length and can no longer protect the chromosomes from damage. (In fact, in 1961, in a paradigm-shifting discovery, Leonard Hayflick, a Wistar researcher, demonstrated that human cells derived from embryonic tissues can only divide about 50 times before dying out. This number has come to be known as the “Hayflick limit.”)

Significant links have begun to emerge between the integrity of telomeres and both aging and cancer. Production of telomerase, an enzyme that partially repairs and lengthens telomeres after each shortening, decreases almost entirely in healthy cells, but increases in cancerous cells.  In fact, activation of telomerase is associated with nearly all human cancers.

Wistar researchers have been involved in telomere and telomerase research for years, and some recent advances here could have a profound impact on how we view and treat disease. 

Assistant Professor Emmanuel Skordalakes, Ph.D., and colleagues recently determined the structure of telomerase—a landmark discovery that could ultimately lead to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies. 

Able to visualize the structure of the enzyme, the team is searching for small molecules that will “fit” the enzyme and inhibit its function of replicating  telomeres in cancer cells, stopping tumor growth in its tracks.

The laboratory of Professor Paul Lieberman, Ph.D., has shown that a large type of RNA (ribonucleic acid) called TERRA interacts with several proteins in the telomeres and plays a central role in helping to maintain them.  

Manipulating TERRA may represent a new way to treat disease. “By managing TERRA levels,” says Lieberman, “we have the potential to regulate cellular aging and to impair the functioning of cancer cells.”