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Little Known DNA Repair Enzyme May Be A Tumor Suppressor Gene

Researchers at the University of Pittsburgh have demonstrated that loss of DNA // repair enzyme’s activity in mouse cells leads to dramatic chromosomal instability.

The DNA in our cells is constantly subject to environmental, chemical and cellular impacts. Thanks to nature, our cells contain several enzymes dedicated to detecting and repairing any damage caused by these impacts. Failure of these enzymes to make needed repairs to genes in time can lead to the accumulation of mutations and, eventually, cell death or probably cancer. The activity of some DNA repair enzymes appears to be more crucial than others, particularly in developing embryos.

University of Pittsburgh researchers report in the January 1 edition of Cancer Research that a poorly understood enzyme, DNA polymerase zeta, also known as pol zeta, has the uncanny ability to give even heavily damaged DNA a new lease of life. When this enzyme is absent in cells that has already 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," says John P. Wittschieben, Ph.D., research instructor in the department of pharmacology, University of Pittsburgh School of Medicine, and first author of the study. "Its loss in animal cells drastically affects the development of chromosomal stability, 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 accurate copies of strands of DNA, damaged areas, called lesions, can bring this replication machinery to a complete halt in certain areas. In the last few years, scientists have learned of the existence of several so-called lesion-replicating polymerases that can overcome th
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