Structural basis for processive DNA synthesis by yeast DNA polymerase ε

Abstract

DNA polymerase ε (Pol ε) is a high-fidelity polymerase that participates in leading-strand synthesis during eukaryotic DNA replication in eukaryotic cells. The 2.2 Å ternary structure of the 142 kDa catalytic core of Pol ε from Saccharomyces cerevisiae in complex with DNA and an incoming nucleotide has recently been determined [1]. The structure provides information about the selection of the correct nucleotide and the positions of amino acids that might be critical for proofreading activity. Pol ε has the highest fidelity among B-family polymerases despite the absence of an extended β-hairpin loop that is required for high-fidelity replication by other B-family polymerases. Moreover, the catalytic core has a new domain (i.e. the P-domain) that allows Pol ε to encircle the nascent double-stranded DNA and enhance processifivity of the polymerase. The structure provides valuable insights into the similarities and differences between Pol ε and other B-family polymerases, and suggests possible mechanisms responsible for the high processivity and fidelity of Pol ε.