Somatic mutation hotspots correlate with DNA polymerase η error spectrum

Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs R (G) under bar YW and W (A) under bar were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched W (A) under bar were preferentially found in one DNA strand and R (G) under bar YW hotspots were found in both strands, Analysis of base-substitution hotspots in DNA polymerase error spectra showed that 33 of 36 hotspots in the human polymerase eta spectrum conformed to the W (A) under bar consensus. This and four other characteristics of polymerase eta substitution specificity suggest that errors introduced by this enzyme during synthesis of the nontranscribed DNA strand in variable regions may contribute to strand-specific somatic hypermutagenesis of immunoglobulin genes at A-T base pairs.