RNase H1 and H2 Are Differentially Regulated to Process RNA-DNA Hybrids

Abstract

Summary: RNA-DNA hybrids are tightly regulated to ensure genome integrity. The RNase H enzymes RNase H1 and H2 contribute to chromosomal stability through the removal of RNA-DNA hybrids. Loss of RNase H2 function is implicated in human diseases of the nervous system and cancer. To better understand RNA-DNA hybrid dynamics, we focused on elucidating the regulation of the RNase H enzymes themselves. Using yeast as a model system, we demonstrate that RNase H1 and H2 are controlled in different manners. RNase H2 has strict cell cycle requirements, in that it has an essential function in G2/M for both R-loop processing and ribonucleotide excision repair. RNase H1, however, can function independently of the cell cycle to remove R-loops and appears to become activated in response to high R-loop loads. These results provide us with a more complete understanding of how and when RNA-DNA hybrids are acted upon by the RNase H enzymes. : RNase H enzymes eliminate the RNA moiety of RNA-DNA hybrids. Lockhart et al. demonstrate that the post-replicative expression of RNase H2 is both necessary and sufficient for effective RNA-DNA hybrid processing. RNase H1 does not have defined cell cycle requirements but rather responds to RNA-DNA hybrid-induced stress. Keywords: RNA-DNA hybrid, R-loop, ribonucleotide excision repair, RNase H1, RNase H2, cell cycle