ADAR deaminase A-to-I editing of DNA and RNA moieties of RNA:DNA hybrids has implications for the mechanism of Ig somatic hypermutation

Abstract

The implications are discussed of recently published biochemical studies on ADAR-mediated A-to-I DNA and RNA deamination at RNA:DNA hybrids. The significance of these data are related to previous work on strand-biased and codon-context mutation signatures in B lymphocytes and cancer genomes. Those studies have established that there are two significant strand biases at A:T and G:C base pairs, A-site mutations exceed T-site mutations (A >> T) by 2.9 fold and G-site mutations exceed C-site mutations (G >> C) by 1.7 fold. Both these strand biases are inconsistent with alternative “DNA Deamination” mechanisms, yet are expected consequences of the RNA/RT-based “Reverse Transcriptase” mechanism of..