title: Structural basis for processive DNA synthesis by yeast DNA polymerase ɛ.
abstract: DNA polymerase ɛ (Pol ɛ) is a high-fidelity polymerase that has been shown to participate in leading-strand synthesis during DNA replication in eukaryotic cells. We present here a ternary structure of the catalytic core of Pol ɛ (142 kDa) from Saccharomyces cerevisiae in complex with DNA and an incoming nucleotide. This structure provides information about the selection of the correct nucleotide and the positions of amino acids that might be critical for proofreading activity. Pol ɛ 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 that allows Pol ɛ to encircle the nascent double-stranded DNA. Altogether, the structure provides an explanation for the high processivity and high fidelity of leading-strand DNA synthesis in eukaryotes.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hogg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Osterman
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Göran O
authors.initials: GO
authors.lastname: Bylund
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Rais A
authors.initials: RA
authors.lastname: Ganai
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Else-Britt
authors.initials: EB
authors.lastname: Lundström
authors.affiliation: Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: A Elisabeth
authors.initials: AE
authors.lastname: Sauer-Eriksson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Erik
authors.identifier: 0000000285266224
authors.initials: E
authors.lastname: Johansson
mesh_terms: D020134:Catalytic Domain; D004257:DNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
chemical_list: D004257:DNA Polymerase II