Fig. 4: The POLγB position differs in the human and mouse error-editing conformers.

a Overview of mPolγ (DNA omitted). Non-conserved residues between human and mouse POLγ are shown in orange. Most non-conserved residues are clustered in POLγB and the L-helix. b Overlaid hPOLγ (PDB: 8D42) and mPolγ error-editing conformers. The position of DNA, hPOLγA and mPolγA subunits are nearly identical in the two structures. However, the hPOLγB is shifted compared to both the distal and proximal mPolγB subunits. The L-helix in POLγA is also shifted as it interacts with POLγB. The DNA is colored gray (human) or beige (mouse). c–e Analysis of the shift between the POLγB subunits. The shift is less prominent in the proximal subunit region which interacts with the POLγA AID subdomain (c, d), with a small shift of 2–4 Å. However, peripheral regions, relative to the AID contact surface, experience a larger shift (8–10 Å) due to a rotation of ~10° (d, e). f Comparison of the POLγB subunits, the AID subdomain and the thumb helix in the R and E conformers in mouse. The region is stable and moves as a rigid body during the transition from replication to error-editing mode. g Comparison of the POLγB subunits, the AID subdomain and the thumb helix in the R and E conformers in human. A shift can be observed in the AID subdomain (4 Å) and the distal POLγB monomer (2–3 Å). The region is thus more flexible than its mouse counterpart during the transition from replication to error-editing mode. h Steady-state kinetics of dNTP incorporation was determined in the mouse system (mAmB), the human system (hAhB) and mixtures of human POLγA and mouse PolγB (hAmB), or mouse PolγA and human POLγB (mAhB) (mean ± s.d.; n = 3 technical replicates). i Steady-state kinetics of dNTP incorporation in human and mouse POLγA alone (mean ± s.d.; n = 3 technical replicates). j Kinetic parameters were obtained from the experiments in (h) and (i) (mean ± s.e.m.; n = 3 technical replicates). Source data are provided as a Source Data file.