Structure of the Catalytic Core of S. cerevisiae DNA polymerase η: Implications for translesion DNA synthesis

DNA polymerase η is unique among eukaryotic polymerases in its proficient ability to replicate through a variety of distorting DNA lesions. We report here the crystal structure of the catalytic core of S. cerevisiae DNA polymerase η, determined at 2.25Å resolution. The structure reveals a novel polydactyl right hand-shaped molecule with a unique polymerase-associated domain. We identify the catalytic residues and show that the fingers and thumb domains are unusually small and stubby. In particular, the unexpected absence of helices "O" and "O1" in the fingers domain suggests that openness of the active site is the critical feature which enables DNA polymerase η to replicate through DNA lesions such as a UV-induced cis-syn thymine-thymine dimer.