( Scientists have determined the detailed...)Groovy protein essential for promoting cancer development

Scientists have determined the detailed structure of an essential piece of the telomerase enzyme, an important contributor to the vast majority of human cancers. Understanding the physical shape of the protein has led to a better understanding of how it acts to immortalize cells ?and should help scientists design broadly effective cancer drugs.

Until now, the lack of detailed structural information about the enzyme has hindered progress in developing agents to inhibit it, say the researchers, who published their findings in an advance online publication in Nature Structural & Molecular Biology on February 5, 2006. Howard Hughes Medical Institute President Thomas R. Cech, whose laboratory is at the University of Colorado at Boulder, led the study, conducted with colleagues Steven A. Jacobs and Elaine R. Podell.

Cancer researchers have long sought a way to subdue telomerase, an enzyme whose excessive activity contributes to the unchecked growth of as many as 90 percent of human tumors. The enzyme is vital for some rapidly dividing cells ?such as those in a developing embryo ? where it extends telomeres, the regions of highly repetitive DNA found at the ends of chromosomes. In most healthy adult cells, telomerase is shut off, and telomeres slowly shrink during cell division ?a normal process that helps limit cells' lifespan. Cancer cells, however, usually find a way to turn telomerase back on, achieving a dangerous immortality.

"Getting telomeres replicated again is required for carcinogenesis to proceed," Cech explained. "It's an essential step in the development of cancer, and that makes it of a lot of interest therapeutically, because it is a target that could impact a wide variety of cancers."

Telomerase inhibitors have been in clinical development for many years, but, Cech said, progress has been slow. "The development of anti-telomerase chemotherapeutics has been challenged by the fact that there was no structural basi
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Source:Howard Hughes Medical Institute

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