Structure of the catalytic core of S-cerevisiae DNA polymerase eta: 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 repor t here the crystal structure of the catalytic core of S. cerevisiae DNA pol ymerase eta, determined at 2.25 Angstrom resolution. The structure reveals a novel polydactyl right hand shaped molecule with a unique polymerase-asso ciated domain. We identify the catalytic residues and show that the fingers and thumb domains are unusually small and stubby. In particular, the unexp ected absence of helices "O" and "O1" in the fingers domain suggests that o penness of the active site is the critical feature which enables DNA polyme rase eta to replicate through DNA lesions such as a UV-induced cis-syn thym ine-thymine dimer.