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PCR Cloning and Subcloning> | … APOBEC3A and APOBEC3B cDNA were synthesized by GenScript with a beta-globin intron and a Flag tag at C-terminus. The plasmid expressing APOBEC3A-Flag, and APOBEC3B-Flag were generated by inserting the cDNA into pDEST53 vectors using the Gateway Cloning … | Get A Quote |
APOBEC mutagenesis, a major driver of cancer evolution, is known for targeting TpC sites in DNA. Recently, we showed that APOBEC3A (A3A) targets DNA hairpin loops. Here, we show that DNA secondary structure is in fact an orthogonal influence on A3A substrate optimality and, surprisingly, can override the TpC sequence preference. VpC (non-TpC) sites in optimal hairpins can outperform TpC sites as mutational hotspots. This expanded understanding of APOBEC mutagenesis illuminates the genomic Twin Paradox, a puzzling pattern of closely spaced mutation hotspots in cancer genomes, in which one is a canonical TpC site but the other is a VpC site, and double mutants are seen only in trans, suggesting a two-hit driver e... More