Jesper Svejstrup has unpicked the molecular mechanisms by which cells transcribe their DNA into messenger RNA, and shown how they avoid damage to the DNA during this process. These discoveries are helping to suggest routes by which DNA damage might cause diseases such as cancer.

During transcription, an enzyme known as RNA polymerase II works its way along the DNA, making RNA copies of the codes for proteins by adding nucleotides one by one. Jesper’s work showed that if RNA polymerase II hits DNA damage, the cell first deploys a set of specialised repair molecules to remove the DNA lesion, or — if this fails — destructive proteins (ubiquitylation factors), enabling degradation of the stopped polymerase to allow DNA repair by other means.

Having first demonstrated this principle in yeast, Jesper and his colleagues have gone on to explore the complex molecular relationships between transcription and DNA repair in human cells. They have made new discoveries both on the nature of RNA polymerase II itself, and of factors involved in transcription-associated genome instability and repair.