R-loop disruption triggers irreversible topoisomerase 1-DNA cleavage complex formation during AID-dependent IgH gene diversification - PubMed
4 hours ago
- #Topoisomerase 1
- #R-loop
- #AID
- R-loop disruption leads to irreversible Topoisomerase 1-DNA cleavage complex (TOP1-CC) formation during AID-dependent antibody gene diversification.
- Antisense oligonucleotides (ASOs) targeting noncoding germline transcripts increase DNA cleavage and decrease R-loops, promoting TOP1-CC formation.
- In vitro, RNase H-mediated R-loop degradation enhances positive supercoiling and double-strand breaks with TOP1, even without AID.
- Knockout of Tdp1 suppresses class switch recombination, showing accumulated TOP1-CCs are processed via an alternative pathway for CSR.
- AID-mediated C-to-U editing in R-loops creates unstable G:U wobble pairs, making R-loops sensitive to nuclear RNases and triggering TOP1-CC formation.