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It takes two to tangle: Wistar scientists further unravel telomere biology
Date:11/21/2012

Chromosomes - long, linear DNA molecules are capped at their ends with special DNA structures called telomeres and an assortment of proteins, which together act as a protective sheath. Telomeres are maintained through the interactions between an enzyme, telomerase, and several accessory proteins. Researchers at The Wistar Institute have defined the structure of one of these critical proteins in yeast.

Understanding how telomeres keep chromosomes and by extension, genomes intact is an area of intense scientific focus in the fields of both aging and cancer. In aging, the DNA of telomeres eventually erodes faster than telomerase and its accessory proteins can maintain it, and cells die. In cancer, tumor cells hijack the process, subverting the natural method by which our bodies limit cell growth; cancer cells, then, can grow and multiply unchecked.

One of these accessory proteins, Cdc13, is integral to telomere maintenance and essential for cell viability in yeast, according to researchers at The Wistar Institute. In a study published in the journal Structure, available online now, a team of scientists led by Emmanuel Skordalakes, Ph.D., an associate professor in The Wistar Institute Cancer Center's Gene Expression and Regulation Program, has determined how mutations in a particular region of Cdc13 can lead to defects in telomeres that could jeopardize DNA.

Cdc13 normally functions as a matched-set, where two copies of the protein form what is known as a dimer. Skordalakes found that mutations in a region of Cdc13 (called OB2) prevent Cdc13 copies from binding to each other. The findings help explain the biology of this key telomere maintenance protein, and may eventually lead to novel anticancer therapeutic if their findings translate to a similar molecular system used to maintain human telomeres, Skordalakes says.

"If we could target the OB2 region of Cdc13, for example, it would throw a wrench in the works of telo
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Contact: Greg Lester
glester@wistar.org
215-898-3934
The Wistar Institute
Source:Eurekalert

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