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Novel Mechanism For DNA Replication Discovered

Since the discovery of the structure of DNA by James Watson and FrancisCrick in 1953, the paradigm for DNA replication has stated that the DNA itself codes for the appropriate pairings for replication. In other words, if a guanine base is on the original strand of DNA then its partner, a cytosine base, will pair to it on the replicated strand. In a study published in this week's issue of Science, researchers from Mount Sinai School of Medicine report on the first instance in which a protein, rather than the DNA, provides the coding information.

The study offers a specific mechanism by which cells cope with some ofthe most destructive carcinogens in the environment, including those incigarette smoke. Many of these carcinogens preferentially damage DNA atguanine -- one of the four bases in DNA -- blocking, in some cases, theability of the guanine to partner with cytosine, which can lead tomistakes during replication.

Aneel Aggarwal, PhD, and Deepak Nair, PhD, of the Department ofPhysiology and Biophysics at Mount Sinai School of Medicine and theircolleagues at University of Texas Medical Branch, Galveston discoveredthat a protein called Rev1 DNA polymerase itself codes for a cytosineto be placed on the replicating strand. The cytosine is inserted basedupon the coding information in Rev1 regardless of whether a guanine oranother base is present on the DNA.

"This is the first time we have seen a protein serving as a templatefor DNA synthesis," said Dr. Aggarwal. "This provides an entirely newmechanism by which cells can replicate through DNA damaged by certaincarcinogens. It thus opens a novel area of study with the potential forinnovative approaches to prevention and treatment of cancer."

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine, September 30, 2005

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