Fig. 1.

Structural model of the POLG holoenzyme in complex with primer-template DNA. In the three-dimensional ternary complex of POLG, the pathogenic clusters in the catalytic core, POLGA, form five distinct functional regions [6]. Upper panel, the structure modeled after PDB structure 4ZTU[39] illustrates the pathogenic clusters of POLGA colored as green for Cluster 1, yellow for Cluster 2, red for Cluster 3, blue for Cluster 4 and cyan for Cluster 5. Lower panel, subclusters are distributed throughout the primary amino acid sequence of the POLGA polypeptide. Subclusters are assigned for each continuous block on the primary amino acid sequence. The accessory subunits, POLGB, are illustrated in light grey (proximal subunit) and dark grey (distal subunit). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)