An enzyme that fixes broken DNA sometimes destroys it instead, Stanford researchers find

PUBLIC RELEASE DATE:

26-Nov-2014

Contact: Rosanne Spector manishma@stanford.edu 650-725-5374 Stanford University Medical Center @sumedicine

Enzymes inside cells that normally repair damaged DNA sometimes wreck it instead, researchers at the Stanford University School of Medicine have found. The insight could lead to a better understanding of the causes of some types of cancer and neurodegenerative disease.

In a paper to be published online Nov. 27 in Molecular Cell, the researchers explain how the recently discovered mechanism of DNA damage occurs when genetic transcripts, composed of RNA, stick to the DNA instead of detaching from it.

Certain enzymes, called endonucleases, are attracted to DNA/RNA hybrids that form when gene transcription goes awry -- and they cut the DNA like scissors to damage it.

The researchers conducted the study with human cells in culture, using molecular biology techniques to turn off specific genes. This allowed them to induce cells to form the hybrids and to see what would happen when various enzymes were inhibited.

"What we found is when we get rid of these endonucleases, we don't see the damage," said Karlene Cimprich, PhD, professor of chemical and systems biology and the paper's senior author. "When those nucleases are present, they cut the DNA in the hybrid."

Both helpful and harmful

What's really interesting, said Cimprich, is these same enzymes are noted for fixing DNA damage. "They take part in the repair of DNA lesions from sunlight and certain chemicals, like those found in cigarette smoke," she said. The structures formed by the hybrid of RNA and DNA are similar to those formed in cells damaged by ultraviolet light.

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An enzyme that fixes broken DNA sometimes destroys it instead, Stanford researchers find