Research Horizons, July 09 - Exposure to environmental carcinogens such as tobacco smoke and ultraviolet radiation can result in various types of DNA damage and subsequently lead to the development of cancer if the damage is not repaired.

Double-strand breaks, in which both strands in the DNA double helix are severed, are particularly hazardous to cells because they can lead to genome rearrangements. And their repair is intrinsically more difficult.

Biologists typically believed that double-strand breaks could only be repaired by homologous intact DNA - until recently, when Francesca Storici, an assistant professor in Georgia Tech's School of Biology, showed that RNA could be used as a template to directly repair DNA in yeast cells. This contradicted the dogma that genetic information had to flow from DNA to RNA.

"Using RNA that naturally resides inside a cell to repair damaged DNA could represent an additional line of defense against DNA damage," says Storici, who is also a Georgia Cancer Coalition Scholar. "The capacity of RNA to record itself into DNA could be the basis of a wholly unexplored process of RNA-driven DNA evolution."

These unique RNA functions may have important implications in gene targeting and gene therapy because RNA molecules mimicking RNA oligonucleotides could be generated directly in the nucleus of targeted cells via transcription from vectors.

Since her initial discovery in yeast, Storici has used RNA to repair bro¬ken chromosomal DNA in human cells in culture and to correct a base defect in the genome of bacterial cells, suggesting that RNA-templated DNA repair is a more general mechanism. She is currently examining exactly how this direct transfer of RNA information to DNA occurs.

"While we can gain a lot of insight from understanding how a cell can repair its DNA, we can also use that information to create a better method for correcting genetic defects," notes Storici.

Her goal is to develop a tool to correct a particular mutation on a specific chromosome while causing minimal damage to the DNA. One way to do that, Storici says, might be to search for factors that facilitate delivery of the targeting molecule to the nucleus and promote the exchange of DNA strands.

To test the tool she develops, Storici is working with and constructing different human cell lines, and monitoring the repair of specific genetic defects with a simple flow cytometry assay.

Given the ability of RNA to transfer genetic information to chromosomal DNA and the possibility of amplifying RNA within cells at will, Storici plans to continue investigating new directions in gene targeting and treatment of cancer and other genetic diseases.