The DNA in our cells is constantly being bombarded by environmental, chemical and cellular insults. Fortunately, our cells contain many enzymes devoted strictly to detecting and repairing any damage caused by these insults. In fact, failure of these enzymes to make needed repairs to genes can lead to the accumulation of mutations and, eventually, cell death or possibly cancer. However, it appears that the activity of some DNA repair enzymes is more critical than others, particularly in developing embryos. University of Pittsburgh researchers report in the Jan. 1 edition of Cancer Research that a poorly understood enzyme, known as DNA polymerase zeta, or pol zeta, has the uncanny ability to give cells with even heavily damaged DNA a new lease on life. Furthermore, when the enzyme is absent in cells that already have growth control problems, the consequences to chromosomes are catastrophic and may lead to cancer.

"Pol zeta appears to be the only one of a group of specialized DNA polymerases that is critical for development in animals," explained John P. Wittschieben, Ph.D., research instructor in the department of pharmacology, University of Pittsburgh School of Medicine, and first author of the study. "Moreover, its loss in animal cells plays a significant role in the development of chromosomal instability, which is a hallmark of cancer. Therefore, we believe its function may be to suppress the development of tumors."

Although DNA polymerases--enzymes responsible for copying, editing and repairing genes and surrounding DNA--generally have the ability to make completely accurate copies of strands of DNA, in certain situations damaged areas, called lesions, can bring this replication machinery to a complete halt. In the last few years, scientists have learned of the existence of a variety of so-called lesion-replicating polymerases that can overcome these replication "stop signs" and keep cells dividing that would otherwise be killed off by their own su
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3-Jan-2006

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