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Study by Tufts biologist provides window into progression of some degenerative diseases

MEDFORD/SOMERVILLE, Mass. A Tufts University study has shed light on how some inherited diseases such as Huntington's and muscular dystrophy develop in humans.

"Our findings show a possible reason that cells with a certain type of mutation (expansion of repetitive DNA) die prematurely," said Catherine Freudenreich, assistant professor of biology at the School of Arts and Sciences at Tufts. "We may be able to use this information to stop or slow the development of some of these degenerative diseases that affect thousands of people every year."

She and her colleagues post-doctoral fellow Mayurika Lahiri and former Tufts undergraduate researchers Tanya Gustafson and Elizabeth Majors published their findings, "Expanded CAG repeats activate the DNA damage checkpoint pathway" in the July 23 issue of the journal Molecular Cell.

Freudenreich, a molecular biologist, studies the unstable elements in the human genome, particularly the type of unstable element called "trinucleotide repeat sequences," whose expansion causes numerous human genetic diseases such as Huntington's disease (a degenerative neurological disease) and myotonic dystrophy (a type of muscular dystrophy). There are more than 15 repeat expansion diseases, all of which are of special interest because they are caused by a highly unusual DNA mutation, one in which a repetitive DNA sequence expands from a small number of copies to a larger number. For example, 20 copies of a DNA sequence (such as CAG) could expand to 70 or 100 copies to cause disease.

With a grant for more than $1 million from the National Institutes of Health, Freudenreich's team investigated whether the presence of expanded repeats in a cell is recognized by the cell as damage and, if so, whether the cell activates the surveillance system that facilitates repair (called the "DNA damage checkpoint pathway"). They found that the proteins that signal that DNA damage is present are activated when a cell contains
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Contact: Siobhan Houton
siobhan.houton@tufts.edu
617-627-5906
Tufts University
22-Jul-2004


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