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Wayne State Researchers Report a Possible 'Proofreading' Step in DNA Synthesis by Observing Single Molecules of DNA Polymerase
Date:12/3/2009

Research could lead to an understanding of how accurate DNA replication occurs to prevent mutations known to result in cancer and genetic diseases

DETROIT, Dec. 3 /PRNewswire-USNewswire/ -- Wayne State researchers have for the first time observed the movement of a single molecule of DNA polymerase as it incorporates nucleotides one by one. More significantly, they have identified a previously unknown step that they speculate is part of the proofreading process known to prevent the polymerase from producing cancer-causing mutations.

Louis Romano, Ph.D., professor of chemistry, and David Rueda, Ph.D., assistant professor of chemistry in the College of Liberal Arts and Sciences, were published in the Dec. 4, 2009 early edition of the Proceedings of the National Academy of Sciences for their observation. In addition, Thomas Christian, a former WSU chemistry graduate student who is now a postdoctoral associate at Yale University, played a key role in the study.

During DNA replication, DNA polymerase incorporates nucleotides into a DNA chain using the strand of the parental DNA as a template to produce two identical double-stranded product DNA molecules. To maintain proper function of the daughter cells, it is crucial that this process be carried out accurately, and the structure of DNA polymerases have evolved so that they only make a mistake once in ~100,000 nucleotides incorporated. An integral part of this process is the ability of most DNA polymerase to remove incorrectly incorporated nucleotides in a process referred to as proofreading. Rueda and Romano believe that they have identified a new step in the proofreading process that helps maintain the incredible accuracy of DNA replication. This process prevents mutations that can lead to potentially deadly diseases such as cancer.

"DNA polymerase has the extremely important job of building DNA accurately," Romano said. "It is fundament
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SOURCE Wayne State University
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