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. 2023 Oct 3;43(10):BSR20222591. doi: 10.1042/BSR20222591

Figure 3. PCNA ubiquitination in the translesion synthesis and template switching pathways.

Figure 3

PCNA monoubiquitination promotes polymerase switching to activate the translesion synthesis pathway (TLS) and enable the bypassing of problematic lesions. Under replication stress, RPA-coated ssDNA recruits a complex of RAD18 and RAD6, leading to PCNA monoubiquitination at K164. This modification disrupts the affinity of PCNA for B-family DNA polymerases (Polδ and Polε) and increases its affinity for specialized Y-family polymerases (including Polη, Polι, Polκ, and Rev1); these events lead to error-prone TLS. In template switching (TS), following the initial RAD6/RAD18-dependent monoubiquitination of PCNA at K164, UBC13-MMS2, and RAD5 are required to generate K63-linked polyubiquitin chains. However, the exact details of TS following PCNA polyubiquitination remain unknown.