DNA secondary structures in BCL2 and MYC elicit activation-induced cytidine deaminase binding and activity - PubMed
3 hours ago
- #AID
- #oncogenic mutagenesis
- #DNA secondary structures
- Activation-induced cytidine deaminase (AID) targets cytosines in immunoglobulin hotspots but also at nonimmunoglobulin sites, leading to oncogenic mutagenesis.
- AID binds and deaminates G4 structures in the BCL2 and MYC promoters, which are associated with lymphoma.
- Specific cytosines in the BCL2 G4 structure are deaminated by AID, with position-dependent activity observed.
- The i-Motif, found in the complementary DNA to the G4, is identified as a novel determinant for AID interaction.
- AID paralogs (A3C, A3A, A2) show differential binding and activity influenced by DNA secondary structures.
- Mutation of AID residue glutamine 135 to alanine disrupts both binding and deamination activity.
- The study suggests that DNA secondary structures in oncogene promoters may recruit AID to off-target sites.