Translesion replication across a UV-induced TT dimer
The replicative polymerase viewed as a right hand (thumb: #1, palm: #2, finger: #3), synthesizes DNA by "induced-fit" mechanism using PCNA (homotrimer) as a sliding clamp.
Specialized polymerases, such as those from the Y family (polη, polι, and polκ), a B-family polymerase, can insert nucleotides opposite the damaged bases and/or extend the resulting 3′ termini.
Translesion polymerases synthesize DNA with low fidelity and processivity. They interact with Rev1, a dCMP transferase from the Y-family.
Y-family polymerases are characterized by more open active site than replicative polymerases and have an additional "little finger" domain (marked with *) and are stimulated via interactions with PCNA.
Blockage of the replication fork activates Rad6/Rad18, which monoubiquitinates PCNA. This causes displacement of the replicative polymerase.
Polη is recruited by Rad18 to the site of the blocked fork where it interacts with monoubiquitinated PCNA and replicates past the damaged bases relatively accurately.
Following a polymerase switch, DNA synthesis is resumed by the more possessive and accurate replicative polymerase.
