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Protein clamps tight to telomeres to help prevent aging ... and support cancer
Date:9/16/2010

if such repair proteins fuse the ends of two chromosomes together, for example. Secondly, Cdc13 recruits telomerase and related proteins to place in order to lengthen the telomeres.

When the researchers introduced mutations into Cdc13 that prevented the protein from forming a dimer, it caused the telomeres to shorten, which would hasten the demise of the yeast cells. When they created mutations that prevented Cdc13 dimers from binding to DNA, it had the effect of excessively lengthening telomeres, an act the researchers attribute to the notion that Cdc13 helps regulate the ability of DNA-replication enzymes to access telomeres.

"The complex role of Cdc13 underscores the unique nature of telomeres and the fine balance between normal cell division and cancer," said Skordalakes.

Telomeres are important to cell division because they serve as sort of a timing mechanism that can, in effect, limit the number of times a normal cell can divide. As each cell divides, it must first replicate or copy the DNA of its chromosomes in exacting detail.

However, the proteins in cells that make this replication possible physically cannot copy the last few base units of DNA at the tips of the chromosomes, which effectively shortens the telomere each time a chromosome is copied. Without telomeres to serve as a buffer, a chromosome could conceivably lose a functioning gene as it is copied. This natural "lifespan" of cells was first identified in the 1960s as the Hayflick Limit, named after its discoverer, Leonard Hayflick, Ph.D., then a Wistar scientist.

In 2008, the Skordalakes laboratory was the first to determine the 3-D structure of the catalytic subunit of the enzyme telomerase, which functions to tack on the short stretches of DNA at the telomeres that the cell's main DNA-replicating enzymes miss. The act of preserving telomeres through telomerase is a hallmark of only certain cells, particularly those in developing embryos. In adu
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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