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NIEHS Researchers Identify Enzyme Critical in DNA Replication

BETHESDA, Md., July 5, 2007--In this weeks issue of Science, researchers from the National Institute of Environmental Health Sciences (NIEHS) and Umeö University in Sweden report an important discovery about a critical new role that an enzyme called DNA polymerase epsilon plays in replicating DNA in higher organisms such as yeast and perhaps even humans.

The study places us one step closer to understanding the origins of genome instability that underlie certain environmental diseases in humans, said NIEHS Director David A. Schwartz, M.D. NIEHS is part of the National Institutes of Health.

The research was conducted by Zachary Pursell, Ph.D. and Thomas A. Kunkel, Ph.D., at NIEHS in collaboration with Erik Johansson, Ph.D. and colleagues at Ume? University.

The researchers used an innovative strategy to demonstrate that in bakers yeast, DNA polymerase epsilon has a primary role in replicating the leading strand of DNA. DNA polymerase epsilon was found to be a key determinant of genome stability and of cellular responses to DNA damage resulting from exposures to environmental stress.

The researchers built on fundamental discoveries on the structure and replication of DNA made by Nobel laureates James Watson, Francis Crick and Arthur Kornberg.

When Watson and Crick first described the structure of DNA in 1953, they pointed out that the two DNA strands, which are referred to as leading and lagging, pair with each other to form the now familiar double helix.

Shortly thereafter, Kornberg and colleagues discovered the first enzymes capable of replicating DNA, a process required to make new genomes for cell division. These enzymes, called DNA polymerases, were shown to copy the two DNA strands in only one of two possible directions. One strand of the double helix must be replicated first by a dedicated leading strand polymerase, followed slightly thereafter by replication o
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