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Tufts biologists find another clue to the origins of degenerative diseases
Date:4/11/2011

MEDFORD/SOMERVILLE, Mass. -- For years, researchers in genome stability have observed that several neurodegenerative diseasesincluding Huntington's diseaseare associated with cell-killing proteins that are created during expansion of a CAG/CTG trinucleotide repeat.

In research published in the March 17 online edition of the journal PLoS Genetics, Tufts University biologist Catherine Freudenreich, and then-graduate student Rangapriya Sundararajan show that cell death in yeast can also result from the process by which the cell repairs damage that occurs within a repeated CAG/CTG sequence.

The findings provide additional insight into the causes of some neurodegenerative diseases. "This represents a new way in which the expanded repeats may be causing cell death that leads to the disease," says Freudenreich. , associate professor of biology at the School of Arts and Sciences at Tufts University "The expanded DNA in and of itself can be toxic to cells."

Scientists have observed that Huntington's disease, myotonic dystrophy and multiple subtypes of spinal cerebella ataxia are caused when the number of repeats at the disease locus exceeds a stability threshold.

For Huntington's disease, the threshold is 38 to 40 repeats. Myotonic dystrophy results when there are close to 200 repeats.

When these expanded repeats occur, the abnormal DNA is copied faithfully into ribonucleic acid, the chemical cousin of DNA. In myotonic dystrophy the errant RNA has a toxic effect because it grabs onto and holds hostage certain proteins, preventing them from carrying out the myriad functions that are vital to the cell.

In Huntington's disease and the ataxias, the RNA serves as a blueprint for an abnormal protein that contains an excessive amount of an amino acid called glutamine.

In her experiment, Freudenreich found a cause of cell death that arises from a DNA checkpoint response.

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Contact: Alex Reid
alexander.reid@tufts.edu
617-627-4173
Tufts University
Source:Eurekalert

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