Fig. 1: Base-pairing and specificity of 8-oxodGTP insertion.
From: Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide
a Base-pairing of dGTP and 8-oxodGTP in the pol μ active site. The anti-conformations of undamaged dGTP and template cytosine (Ct) enable Watson–Crick base-pairing (bottom left). The steric and electrostatic clash (red circle) between O8 and Pα of 8-oxodGTP(anti) opposite Ct(anti) discourages adoption of the anti-conformation (top left). Adoption of the syn-conformation enables favorable 8-oxodGTP Hoogsteen base-pairing with template adenine (At) in anti-conformation (top right). Incorporation of dGTP(anti) opposite At(syn) creates unfavorable (red circle) interactions in the template strand (bottom right). Watson–Crick hydrogen bonding is shown with blue dashed lines, while Hoogsteen interactions are shown as red dashed lines. The conformation of each base is indicated in parentheses. b Catalytic efficiencies of dGTP and 8-oxodGTP insertion opposite templates C (Ct) or A (At) in the presence of Mg2+ (left panel) or Mn2+ (right panel) (see Supplementary Table 1). Catalytic efficiency (kcat/KM, in μM−1 min−1) is indicated as a blue line for insertion opposite Ct and as a red line for insertion opposite At. Error bars shown represent standard errors (S.E.) derived from triplicate measurements.
