Local mutation preferences for UV-A and APOBEC3B-induced mutagenesis. Top row (a): ultraviolet (UV)-A crosslinks adjacent pyrimidine bases (lesion depicted by double dash sign (=)). Several DNA polymerases will bypass this lesion by inserting two adenines. Excision repair or another round of DNA replication will convert these C/A mispairs into C-to-T transition mutations. Bottom row (b): APOBEC3B (A3B) catalyzes the hydrolytic deamination of single-stranded DNA cytosine into uracil (lesion depicted in biochemically preferred 5’-TCA context). Uracil in DNA is recognized as a ‘normal’ thymine by DNA polymerases, and it therefore templates the insertion of an adenine in the complementary DNA strand. Uracil base excision repair or another round of DNA replication will convert the U-A base pair into a C-to-T transition mutation. Additional mutagenic outcomes are depicted in Figure 3.