FIGURE 7:

A proposed model depicting the ordered assembly and switch of mammalian TLS polymerases in response to UV irradiation. On UV irradiation, the replication machinery is stalled at the damaged template and invokes PCNA monoubiquitination by the HR6A/HR6B–Rad18 complex. Monoubiquitinated PCNA independently recruits both Rev1 and Polη to the damage site, and Polη is able to insert dAs across the thymine dimer with relatively high fidelity with or without assistance from Rev1. Meanwhile, Rev1 is able to recruit Polζ to the damage site probably through its interaction with the Rev7 subunit, and the Rev1–Polη interaction brings Polζ into proximity to replace Polη for primer extension. It is noted that for a different type of DNA damage, another preferred TLS polymerase may replace Polη for a similar reaction. This model also predicts that in the absence of Polη, Rev1 (or another TLS polymerase) may serve to perform translesion insertion, followed by Polζ extension. All three subunits of PCNA are monoubiquitinated in the diagram for convenience, and we understand that whether this is required for TLS is subject to debate.