ETH researchers decode the mechanism of DNA repair

(CONNECT) Jacob Corn, ETH Professor of Genome Biology, and his team have gained fundamental insights into how cells constantly repair their DNA. This is not just about the possible reactions to external exposure to toxins or radiation, but about their day-to-day survival.

For their recently published study, the team examined 150,000 different combinations of inactivated gene pairs of the 500 or so genes that are known to be central to DNA repair. According to an ETH report, the idea behind this was that it is usually not enough to inactivate a single gene in order to detect an effect. This is because another gene often takes over the missing function.

With around 5000 such inactivated gene pairs, the cells lost their ability to mend the genetic material. After a certain time, they are no longer viable. In the course of their work, the researchers discovered a host of previously unknown interdependencies that are apparently necessary for the cells to thrive.

They also found new clues for cancer therapy. In some of them, some of the more than 500 repair genes have already been switched off due to mutations. "Our search has shown which additional genes need to be inactivated in order to prevent the growth of cancer cells," says first author John Fielden. These potential weak points now need to be tested.

"We have shown which paths lead through the dark forest," says Corn. "Now it's easy to follow these paths." To ensure that this work bears fruit as soon as possible, the team has published its results online. ce/mm