Translesion synthesis (TLS) is a kind of DNA repair that maintains the stability of the genome and ensures the normal growth of life in cells under emergencies. Y-family
DNA polymerases, as a kind of error-prone
DNA polymerase, mainly perform TLS. Previous studies have suggested that the occurrence of
tumors is associated with the overexpression of human
DNA polymerase of the Y family. And the combination of Y-family
DNA polymerase inhibitors is promising for
cancer therapy. Here we report the functional and structural characterization of a member of the Y-family
DNA polymerases, TTEDbh. We determine TTEDbh is an extreme TLS polymerase that can cross oxidative damage sites, and further identify the
amino acids and novel structures that are critical for
DNA binding, synthesis, fidelity, and oxidative damage bypass. Moreover, previously unnoticed structural elements with important functions have been discovered and analyzed. These studies provide a more experimental basis for further elucidating the molecular mechanisms of
DNA polymerase in the Y family. It could also shed light on the design of drugs to target
tumors.