RNases H participate in the replication and maintenance of genomic DNA. RNase H1
cleaves the RNA strand of RNA/DNA hybrids, and RNase H2 in addition hydrolyzes
the RNA residue of RNA-DNA junctions. RNase H3 is structurally closely related
to RNases H2, but its biochemical properties are similar to type 1 enzymes. Its
unique N-terminal substrate-binding domain (N-domain) is related to TATA-binding
protein. Here, we report the first crystal structure of RNase H3 in complex with
its RNA/DNA substrate. Just like RNases H1, type 3 enzyme recognizes the 2'-OH
groups of the RNA strand and detects the DNA strand by binding a phosphate group
and inducing B-form conformation. Moreover, the N-domain recognizes RNA and DNA
in a manner that is highly similar to the hybrid-binding domain of RNases H1.
Our structure demonstrates a remarkable example of parallel evolution of the
elements used in the specific recognition of RNA and DNA.
