Mechanism controlling DNA damage response has potential novel medical ap...( Investigators at St. Jude Children's Re...),Health

Investigators at St. Jude Children's Research Hospital have discovered a previously unrecognized mechanism that controls a key protein linked to the cell's response to stress - a finding that holds promise for new ways to enhance cancer therapies or protect cells from dying after exposure to damaging chemicals or radiation.

The gene for this protein, called p53, is the most commonly mutated gene in human cancer; and it plays a critical role in helping cells respond to stress, especially stresses that damage DNA, according to researchers.

Previously, the rise in the level of p53 in cells whose DNA had been damaged was thought to be due only to a decrease in the rate at which the p53 protein is broken down in the cell. The St. Jude study showed that the level of p53 protein synthesis increases following DNA damage. This discovery suggests that scientists can use this newly recognized mechanism to modulate p53 function in the cell in order to control whether cells in the body mutate, and whether cells live or die after DNA damage. A report on this work appears in the October 7 issue of the journal Cell.

If a cell has been damaged, p53 protects the body by either preventing that cell from dividing or triggering a cascade of molecular signals that causes that cell to commit suicidea process called apoptosis. In this way, p53 rids the body of useless cells and prevents cells with potentially cancer-causing mutations from multiplying and spreading. Failure of a cell to activate p53 function after DNA damage can contribute to the generation of genetically altered cells that leads to cancer.

The St. Jude team showed that the competing proteins, ribosomal protein L26 (RPL26) and nucleolin, vie for control of the messenger RNA (mRNA) that codes for p53. mRNA is the decoded form of a gene that acts like a blueprint that the cell's protein-making machinery (ribosomes) use to make a specific protein. Researchers identified a region of the mRNA, called the 5
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Contact: Carrie Strehlau
Carrie.Strehlau@stjude.org
901-495-2295
St. Jude Children's Research Hospital
6-Oct-2005

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