Structures of DNA Polymerases caught processing size-augmented nucleotide probes

Abstract

The integrity of the genome relies primarily on the ability of DNA polymerases to efficiently catalyze selective DNA synthesis according to the Watson Crick rule in a templatedirected manner during DNA replication, repair, and recombination. Remarkably, some DNA polymerases achieve selective information transfer to the offspring in line with the Watson Crick rule with intrinsic error rates as low as one mistake per one million synthesized nucleotides.[1] This is far below the value that would be expected based on the energetic differences between canonical (i.e. Watson Crick) and noncanonical nucleobase pairing.[1] Geometric factors are widely cited to govern DNA polymerase selectivity.[1] Thus, high-fidelity DNA polymerases are believed to mostly select the canonical nucleotide based on close steric complementarity of the nascent base pair to the geometry of the active site of the enzyme.