a, Possible base editing outcomes in mammalian cells. Initial editing results in a U:G mismatch. Recognition and excision of the U by uracil DNA glycosylase (UDG) initiates base excision repair (BER), which leads to reversion to the C:G starting state. BER is impeded by BE2 and BE3, which inhibit UDG. The U:G mismatch is also processed by mismatch repair (MMR), which preferentially repairs the nicked strand of a mismatch. BE3 nicks the non-edited strand containing the G, favouring resolution of the U:G mismatch to the desired U:A or T:A outcome. b, HEK293T cells were treated as described in the Methods. The percentage of total DNA sequencing reads with Ts at the target positions indicated are shown for treatment with BE1, BE2, or BE3, or for treatment with wild-type Cas9 with a 200-nt donor HDR template. c, Frequency of indel formation (see Methods) is shown following the treatment in b. Values are listed in Extended Data Table 1. For b and c, values and error bars reflect the mean and s.d. of three independent biological replicates performed on different days.