Structure and Function of RNase H Enzymes

Abstract

RNase H enzymes are endonucleases that specifically cleave ribonucleotides within an RNA:DNA duplex. RNase H proteins are divided into type 1 and type 2 enzymes based on amino acid sequence similarities, substrate specificity, and structure. Both RNase H1 and RNase H2 enzymes play important roles in DNA replication, repair and transcription, and at least one type of RNase H is found in most organisms. Both RNase H1 and RNase H2 enzymes share a common structural fold of mixed β-sheets surrounded by several helices at their catalytic core. The enzymes utilize a two-metal-ion mechanism of phosphoryl hydrolysis mediated by divalent Mg2+ ions. RNase H1 enzymes are single polypeptide proteins with eukaryotic members containing an additional hybrid-binding domain (HBD). Eukaryotic RNase H2 is a heterotrimeric complex of the RNase H2A, RNase H2B, and RNase H2C proteins that are all necessary for enzymatic activity. Mutations in the human RNase H2 complex result in immune dysfunction.