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Enzyme alerts cell's powerful army to repair DNA damage
Date:9/5/2007

ANN ARBOR, Mich. Scientists know that inside each cell, a little engine called RNA polymerase II does one essential job: It copies instructions from genes in the nucleus that get carried to production units in the rest of the cell to support our daily needs. Now researchers at the University of Michigan Medical School have shown that RNA polymerase II also constantly scans the cells DNA for damage. When certain types of damage in DNA halt the action of RNA polymerase II, a stress signal is generated that alerts a key tumor-suppressor protein called p53.

The activities of p53, a master protein that responds to DNA damage by marshaling hundreds of genes to repair or eliminate damaged cells, have been the subject of thousands of studies. Mutations in the p53 gene occur in more than half of all cancers.

We have come up with a new paradigm for how cells protect themselves against cancer-producing DNA lesions, says Mats Ljungman, Ph.D., a U-M researcher and lead author of a recent study in the Proceedings of the National Academy of Sciences.

Much is known already about p53, but this adds a significant piece of knowledge about how it is activated, Ljungman adds. He is an associate professor in the Department of Radiation Oncology in the Division of Radiation and Cancer Biology at the U-M Comprehensive Cancer Center and associate professor of Environmental Health Sciences at the U-M School of Public Health.

A commentary in the journal praised the U-M study and urged more attention to RNA polymerases as major sensors for all DNA damage response reactions.

Ljungman says the findings have implications for the study of cancer, aging and neurological diseases. Figuring out precisely how cells detect and repair damage is crucial in understanding what goes wrong in cancer, in which harmful mutations can elude the bodys ability to control cell division.

Finding and repairing DNA lesions is a non-stop job for cell
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Contact: Anne Rueter
arueter@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

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