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Protein clamps tight to telomeres to help prevent aging...and support cancer
Date:9/15/2010

The number of times our cells can divide is dictated by telomeres, stretches of DNA at the tips of our chromosomes. Understanding how telomeres keep our chromosomes and by extension, our genomes intact is an area of intense scientific focus in the fields of both aging and cancer. Now, scientists at The Wistar Institute have published the first detailed report on the structure and function of a crucial domain in the protein known as Cdc13, which sustains telomeres by clamping to DNA and recruiting replicating enzymes to the area.

While the nature of this portion of Cdc13 had previously eluded scientists, the Wistar researchers found that two copies of the protein bind together to form what is called a "dimer," and how that dimer physically interacts with DNA, regulating how enzymes called telomerases access and lengthen the telomeres. The study was performed using the yeast gene, however, this essential life process has changed little through evolution, and evidence suggests that the human equivalent of this protein may make a good target for future anticancer drugs. They present their findings in the journal Molecular and Cellular Biology, available online now, ahead of print.

"Cdc13 has a crucial support role in maintaining and lengthening telomeres, which are reduced in length through every round of DNA replication," said Emmanuel Skordalakes, Ph.D., assistant professor in Wistar's Gene Expression and Regulation Program and senior author of the study. "We know that disabling this protein in humans will most likely lead to senescence, which is of particular interest in cancer, because telomere lengthening is one of the ways cancer cells obtain their immortality."

In the present study, Skordalakes and his colleagues detail how Cdc13 serves a dual function in telomere replication. First, it keeps the cells' natural DNA repair mechanisms from mistaking the telomere for a broken stretch of DNA, which could cause genetic mayhem
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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