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Bacterial Protein Structure Hints At Mechanism Of A Class Of Premature Aging Diseases

DURHAM, N.C -- Using a bacterial model system, scientists at Duke University Medical Center have determined the first step in understanding how a new class of genetic flaws may translate into diseases.

Deepak Bastia and Steven White, professors of microbiology at Duke, have determined how a protein, called a replication termination protein (RTP), stops DNA replication in the bacterium Bacillus subtilis, a common experimental organism.

Rather than simply acting as a roadblock to replication, as had been previously thought, RTP is more like a one way door, allowing the DNA replication machinery to move in only one direction along the DNA strand, the researchers said. They said the work has implications for human disease because RTP interacts with a class of proteins known as helicases, which have been shown to be involved in several genetic diseases. Bastia is now starting work on identifying the comparable protein in humans.

The researchers' findings appear in the Nov. 29 issue of the journal Cell. The research was funded by the National Institutes of Health.

RTP has been known to exist for 20 years, but it wasn't until two years ago that its structure was revealed by Bastia and White. "This [recent] work relates structure to function and takes us one step further in understanding how RTP works," Bastia said.

When DNA replicates, it unzips, starting and ending at specific sites. The helicases are responsible for pulling apart the DNA strands, which are twisted in a helical pattern. "RTP ensures that when DNA replicates, it is brought to a neat and accurate finish, and the cell knows that it is time to divide into two," White said.

Recently, helicase malfunction has been found responsible for a class of genetic diseases including Werner's syndrome and Cockayne's syndrome, premature aging syndromes; Bloom's syndrome, a type of dwarfism; and some kinds of skin cancer. Understanding of
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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University
29-Nov-1996


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