Genome-Embedded Ribonucleotides and Genome Instability
Andrew Jackson
MRC Human Genetics Edinburgh, Edinburgh, UK
Our identification of biallelic hypomorphic mutations in three RNase H2 genes1 in the neuroinflammatory
disorder, Aicardi-Goutières syndrome led us to investigate enzyme complex they encode. We
subsequently established this is an important genome surveillance enzyme that removes over 1,000,000
ribonucleotides embedded in the genomic DNA of every replicating mammalian cell. Such
ribonucleotides represent the most common non-canonical nucleotides incorporated into the genome by
replicative polymerases and are an important potential source of genome instability.