polι, a remarkably error-prone human DNA polymerase

• DOI: 10.1101/gad.14.13.1642
• Publication Date: 2021-11-15T03:33:07Z
• Authors: Agnès Tissier; John P. McDonald; Ekaterina G. Frank; Roger Woodgate
• Keywords: DNA clamp; DNA polymerase mu; DNA polymerase II

The Saccharomyces cerevisiae RAD30 gene encodes DNA polymerase eta. Humans possess two Rad30 homologs. One (RAD30A/POLH) has previously been characterized and shown to be defective in humans with the Xeroderma pigmentosum variant phenotype. Here, we report experiments demonstrating that second human homolog (RAD30B), also a novel designate poliota. poliota, is distributive enzyme highly error-prone when replicating undamaged DNA. At template G or C, average error frequency was approximately 1 x 10(-2). Our studies revealed, however, striking asymmetry misincorporation at A T. For example, replicated greatest accuracy, of G, A, C occurring 10(-4) 2 10(-4). In dramatic contrast, most errors occurred T, where was, fact, favored 3:1 over correct nucleotide, T 6.7 10(-1). These findings demonstrate poliota one eukaryotic polymerases reported date exhibits an unusual spectrum vitro.