RNaseH2 plays a role in the maintenance of genome stability

Ribonuclease H (RNaseH) is a family of evolutionally conserved enzymes capable of cleaving the RNA moiety in RNA:DNA hybrid molecules. Eukaryotic cells are provided with RNaseHI and RnaseH2 activities. The main differences between these two enzymes rest in substrate specificity. In fact only RNaseH2 is capable to recognize and cleave a single ribonucleotide in a duplex DNA molecule. Mutations in the RNaseH2 enzyme, are found in a subset of patients suffering of a rare genetic disease, called Aicardi-Goutières Syndrome (AGS). RNA:DNA hybrids are transient intermediates occurring during several biological processes, such as DNA replication, telomere metabolism, retrovirus replication, retroelements mobilization and transcription (i.e. R-loops). These hybrid molecules are physiologically short-lived, but in some conditions they can generate pathological structures that need to be tightly controlled in order to avoid an increase in genomic instability that is known to be linked to cancer predisposition. We are studying the role of RNaseH in controlling genome integrity in normal and replication stress conditions, using S.cerevisiae cells as a model system. Our results indicate that yeast RNaseH mutant cells are sensitive to genotoxic treatments. We have characterized the biological process responsible for this phenotype and we have identified the molecular pathways that allows survival of the RNaseH mutants in the presence of replication stress.