R-loop disruption triggers irreversible topoisomerase 1–DNA cleavage complex formation during AID-dependent IgH gene diversification

knockout cells serve as substrates for CSR through an alternative TOP1-CC processing pathway. Collectively, these results suggest the R-loop destabilization as a critical, hitherto unrecognized intermediary step linking C-to-U editing to TOP1-CC formation. AID-mediated C-to-U editing within R-loops introduces a G:U wobble base pair, which we hypothesize renders R-loops unstable and sensitive to nuclear RNases, leading to R-loop disruption; this disruption consequently induces the TOP1-CCs and results in CSR, as confirmed in this study.