Solution structure of a viral DNA polymerase X and evidence for a mutagenic function

The African swine fever virus DNA polymerase X (ASFV Pol X or Pol X), the s mallest known nucleotide polymerase, has recently been reported to be an ex tremely low fidelity polymerase that may be involved in strategic mutagenes is of the viral genome. Here we report the solution structure of Pol X. The structure, unique within the realm of nucleotide polymerases, consists of only palm and fingers subdomains. Despite the absence of a thumb subdomain, which is important for DNA binding in other polymerases, we show that Pol X binds DNA with very high affinity. Further structural analyses suggest a novel mode of DNA binding that may contribute to low fidelity synthesis. We also demonstrate that the ASFV DNA ligase is a low fidelity ligase capable of sealing a nick that contains a G-G mismatch. This supports the hypothes is of a virus-encoded, mutagenic base excision repair pathway consisting of a tandem Pol X/ligase mutator.