Study Shows Cellular RNA Can Template DNA Repair in Yeast

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Newswise The ability to accurately repair DNA damaged by spontaneous errors, oxidation or mutagens is crucial to the survival of cells. This repair is normally accomplished by using an identical or homologous intact sequence of DNA, but scientists have now shown that RNA produced within cells of a common budding yeast can serve as a template for repairing the most devastating DNA damage a break in both strands of a DNA helix.

Earlier research had shown that synthetic RNA oligonucleotides introduced into cells could help repair DNA breaks, but the new study is believed to be the first to show that a cells own RNA could be used for DNA recombination and repair. The finding provides a better understanding of how cells maintain genomic stability, and if the phenomenon extends to human cells, could potentially lead to new therapeutic or prevention strategies for genetic-based disease.

The research was supported by the National Science Foundation, the National Institutes of Health and the Georgia Research Alliance. The results were scheduled to be reported September 3, 2014, in the journal Nature.

We have found that genetic information can flow from RNA to DNA in a homology-driven manner, from cellular RNA to a homologous DNA sequence, said Francesca Storici, an associate professor in the School of Biology at the Georgia Institute of Technology and senior author of the paper. This process is moving the genetic information in the opposite direction from which it normally flows. We have shown that when an endogenous RNA molecule can anneal to broken homologous DNA without being removed, the RNA can repair the damaged DNA. This finding reveals the existence of a novel mechanism of genetic recombination.

Most newly-transcribed RNA is quickly exported from the nucleus to the cytoplasm of cells to perform its many essential roles in gene coding and expression, and in regulation of cell operations. Generally, RNA is kept away from or removed from nuclear DNA. In fact, it is known that annealing of RNA with complementary chromosomal DNA is dangerous for cells because it may impair transcription elongation and DNA replication, promoting genome instability.

This new study reveals that under conditions of genotoxic stress, such as a break in DNA, the role of RNA paired with complementary DNA may be different, and beneficial, for a cell. We discovered a mechanism in which transcript RNA anneals with complementary broken DNA and serves as a template for recombination and DNA repair, and thus has a role in both modifying and stabilizing the genome, Storici explained.

DNA damage can arise from a variety of causes both inside and outside the cell. Because the DNA consists of two complementary strands, one strand can normally be used to repair damage to the other. However, if the cell sustains breakage in both strands known as a double-strand break the repair options are more limited. Simply rejoining the broken ends carries a high risk of unwanted mutations or chromosome rearrangement, which can cause undesirable effects including cancer. Without successful repair, however, the cell may die or be unable to carry out important functions.

Beginning in 2007, Storicis research team showed that synthetic RNA introduced into cells including human cells could repair DNA damage, but the process was inefficient and there were questions about whether the process could occur naturally.

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Study Shows Cellular RNA Can Template DNA Repair in Yeast