Conformational explorations into DNA polymerase X from African swine fever virus in the presence of oxoG lesions

Originating from the African swine fever virus, DNA polymerase X (pol X) is a 174‐amino‐acid, low fidelity repair polymerase that participates in viral Base Excision Repair (BER). Several studies have shown that polymerases engaged in BER, including pol X's human homologue polymerase β (pol β), operate via an induced fit mechanism. Previous molecular dynamics studies on pol X suggested that this enzyme also undergoes a conformational change upon binding the right nucleotide. In this study, we are exploring several pol X/DNA complexes in which the templating base pair opposite to the incoming nucleotide contains the damaged base 7,8‐Dihydro‐8‐oxoguanine (oxoG). OxoG is one of the major known products of oxidation of DNA by reactive oxygen species (ROS). Since the African swine fever virus's components are in an active state of respiration, it is conceivable that the virus may encounter this common ROS‐induced DNA lesion. Kinetics data have shown that pol X accommodates A opposite to oxoG, with efficiency even higher than the non‐damaged G:C base pair. Thus, the goal of this molecular dynamics study is to explore combinations of oxoG:A, oxoG:G and oxoG:C systems to elucidate, at an atomistic level, the kinetics data. This research was supported in part by the Rose M. Badgeley Charitable Trust.