Structure of the catalytic core of S-cerevisiae DNA polymerase η:: Implications for translesion DNA synthesis

DNA polymerase eta 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 eta, determined at 2.25 Angstrom 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 eta to replicate through DNA lesions such as a UV-induced cis-syn thymine-thymine dimer.