Figure 1.

Mutagenic pathways of SHM. Deamination of C by AID during SHM leads to a specific mutagenic spectrum. The creation of the full SHM spectrum depends on (1) replication opposite template U instructs a template T and generates transitions at C/G. (2) UNG2 dependent TLS generates C/G transversions. UNG2 converts a U into an abasic site. As abasic sites are non-instructive, TLS opposite these sites generates both transitions and transversions. (3) Hybrid pathway between non-canonical mismatch repair (ncMMR) and UNG2 dependent TLS generates transversions at C/G. (4) ncMMR generates the majority of mutations at A/T. (5) UNG2- and PCNA Ubiquitination (PCNA-Ub)- dependent mutations at A/T. This non-canonical long-patch BER pathway generates a minor but significant subset of A/T mutations (~8%).