Newly Discovered Human Protein Provides Important Target For Cancer Therapy

atch. This stopwatch keeps track of the number of cell divisions that occur in any one population of cells over a person's lifetime. Normal cells have a finite replication potential; they can divide only so many times and then they die. In contrast, cancer cells divide and multiply without limit.

Evidence collected by many laboratories indicates that the clock or counting mechanism relies on specialized bits of DNA, called telomeres, at the ends of each human chromosome. In the absence of telomerase enzyme, these specialized end-structures grow shorter with each round of cell division. Eventually, the shortening process reaches a critical stage; the chromosomes become unstable and any further cell division leads to cell death. (This limited allowance for cell divisions may be a significant factor in normal human aging.)

"Cancer cells find a way of switching telomerase activity on, which gives them a tremendous competitive advantage," Dr. Weinberg says. "They have the potential for continuous reproduction in the body or in cell culture--they become immortalized. We want to learn how cancer cells regenerate telomerase function and, at a more fundamental level, how all cells switch telomerase off and on."

Ideal Target for Chemotherapy

The telomerase enzyme is a complex structure containing multiple proteins and an RNA molecule (RNA is a chemical cousin of DNA and, in this case, acts as a template for the production of new telomere segments). Previously, researchers in other laboratories had identified the genes responsible for producing human telomerase RNA and one telomerase-associated human protein, but careful studies of these genes revealed that neither could explain the regulation of telomerase activity: expression of the genes does not correlate with observed levels of telomerase activity in normal or cancerous cells.

Finding the critical catalytic subunit that actually transcribes telomerase's RNA t

Contact: Eve Nichols or Seema Kumar
(617) 258-5183
Whitehead Institute for Biomedical Research

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