AID-dependent genetic alteration mechanism to generate antigen-specific antibodies

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We found that AID down-modulates translation of topoisomerase (Top1). The reduction of Top1 induces aberrant DNA structure in transcribed S regions, resulting in irreversible cleavage by Top1. We propose that AID edits microRNA and edited microRNA down-modulates translation of Top1 mRNA. AID was shown to be expressed not only in lymphoma but also pathogen-induced tumors. We investigated the AID promoter and identified positive and negative regulatory elements, which may explain such AID induction. We examined DNA deamination hypothesis and obtained the following evidence against this hypothesis. 1) AID mutant without DNA deamination activity is proficient for CSR. 2) UNG mutants of the protein interaction domain with normal U removal activity lost CSR activity. 3) APE1 and APE2 deficiency did not reduce CSR.