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Evidence of rapid evolution is found at the tips of chromosomes

In terms of their telomeres, mice are more complicated than humans. That's the finding from a recent Rockefeller University study, which shows that mice have two proteins working together to do the job of a single protein in human cells. The findings, published recently in Cell, suggest that the protein complex that protects chromosome ends may have evolved far more rapidly than previously believed.

Acting as caps on the ends of each chromosome, telomeres are composed of repetitive DNA and shelterin, a protective protein complex protects. Titia de Lange's lab has identified many of the components of shelterin and studies how its components work together to ensure that chromosome ends are not recognized as DNA breaks.

Previous work from the de Lange lab showed that TRF2, a shelterin protein that binds to the duplex part of the telomere, is crucial for telomere protection. Without TRF2, telomeres activate a DNA damage signal and are repaired by the same pathways that act on DNA breaks. TRF2 brings a second shelterin protein, POT1, to the telomeres. Because POT1 binds to single-stranded telomeric DNA present at the very end of the chromosomes, the de Lange lab asked how POT1 contributes to the protection of telomeres.

"We had previously removed TRF2 from mouse cells and seen many dramatic phenotypes," says de Lange, "all of the telomeres ligate together; there is a massive DNA damage response and the cells basically die. We argued that if the function of TRF2 was to bring POT1 to the DNA, then we should observe the same phenotype if we removed POT1."

To determine if this was the case, graduate student Dirk Hockemeyer, the first author of the paper, decided to remove the POT1 gene from mice. Humans have one POT1 gene, so de Lange and Hockemeyer were more than a bit surprised when they found two POT1 genes in the mouse genome. "Both genes are ubiquitously expressed and both are at telomeres," says de Lange. "Nothing prepared us
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Contact: Kristine Kelly
kkelly@rockefeller.edu
212-327-7146
Rockefeller University
1-Aug-2006


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