Project 9 - Brian Luke

Misincorporated ribonucleotide monophosphates (rNMPs) are the most frequently occurring type of endogenous DNA lesion. When not repaired properly, rNMPs lead to neurological disorders and cancer. The aims in this project are designed to understand how and when rNMPs are repaired on a genome-wide scale. We will build on data from the first funding period to elucidate rNMP repair pathways that act independently of the canonical RNase H2 enzyme, these represent potential targets in RNase H2 deficient cancers. Additionally, we will elucidate how RNase H2 acts in a temporal manner at rNMPs. These aims will add critical detail in understanding how the most frequent DNA lesion is repaired to maintain a stable genome.