EASTBIO: Location,location, location: DNA damage sensors which launch protective responses to DNA damage

DNA damage happens at very high frequency in the cells in our bodies – meaning that the instructions for the proper functioning of cells could be altered unless the mistakes are spotted and corrected. We recently started a search for new surveillance factors in human cells that can detect damaged DNA and help to launch the DDR “DNA damage response” that stops secondary consequences of DNA damage such as mutations, disease or cell death (see for example EMBO Journal 40, e108271). Specifically, we screened for factors in cells capable of recognizing damaged DNA inside the nucleus, which we induce experimentally using lasers attached to a confocal microscope. These experiments revealed a range of enzymes that rapidly translocate to damaged DNA, suggesting participation in cellular responses to DNA damage. These enzymes include nucleases, DUBs and helicases. We now wish to understand in detail how these factors recognize damaged DNA and how they participate in DNA repair and other protective responses.

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