Fig. 1.

Mechanisms and preferred substrates for APOBEC3-mediated mutagenesis. Upper panel: APOBEC3s deaminate ssDNA, leaving uracil in the DNA template. Erroneous replication and repair pathways can then generate mutational signatures 2 and 13. Repair by the translesion synthesis (TLS) polymerase REVI generates a C-to-G mutation (signature 13), while repair by other enzymes such as DNA polymerase δ, DNA polymerase ε, and TLS polymerase κ generates a C-to-T mutation (signature 2) [20]. Lower panel: The major mutators among the APOBEC3 superfamily have distinct substrate preferences defined mainly by trinucleotide context and ssDNA secondary structure