To stay healthy, cells must repair their DNA. In most cells, DNA damage is preferentially repaired using a DNA-template to avoid mutations. However, neurons are thought to rely exclusively upon error-prone non-templated repair due to lack of a DNA copy synthesized during cell division. Because DNA is transcribed into RNA, we hypothesize RNA provides an alternative repair-template. Polymerase theta was shown recently to generate DNA from an RNA-template in dividing cells.
We will investigate if polymerase theta enables RNA-templated repair in human neurons, giving insight into the occurrence of (harmful) mutations and feasibility of therapeutic gene editing in the brain.