The enemy within: ribonucleotides, DNA replication and disease
Supervisors: Dr Tom Deegan and Professor Andrew Jackson
Aberrant nucleotides in our DNA cause damage and mutations that can lead to cancer and genetic disorders. The most common, but least studied, are ribonucleotides, with over a million incorporated into the human genome during DNA replication in every cell. We recently discovered a ribonucleotide-associated mutation signature seen in many cancers (Reijns et al, Nature, 2022). However, how removal of embedded ribonucleotides is coordinated with replication remains unclear. This project will use cutting-edge biochemistry (Deegan et al, Mol Cell, 2019) and cell biology to understand what happens when the replisome encounters ribonucleotides, and how unrepaired ribonucleotides lead to DNA damage, mutation and disease.