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Title [sv]
Strukturella och funktionella studier av DNA polymeras epsilon
Title [en]
Structural and functional studies of DNA polymerase epsilon
Abstract [sv]
We showed earlier that DNA polymerase epsilon synthesize leading strand when the yeast genome is duplicated. Now we have solved the first crystal structure of Pol epsilon (2.2 Å resolution). Yeast Pol epsilon (142 kDa catalytic core) is caught in the act of replication, giving information about the selection of a correct nucleotide and the position of aminoacids that may be critical for the proofreading activity of Pol epsilon. Pol epsilon has the highest fidelity among B-family polymerases despite the absence of a beta-hairpin loop that is required for high-fidelity replication by the other B-family polymerases. Instead we show that the catalytic core of Pol epsilon has a novel domain that allows the enzyme to encircle the nascent double-stranded DNA. We will study the function of specific amino acids and domains to understand how Pol epsilon achieves high processivity and high fidelity when synthesizing DNA. We will also study the mechanism of formation of the chemical bond between the incoming nucleotide and the 3´-end of the primer. Functionally interesting mutants will be characterized in vivo by yeast genetics to determine the effects on the replication fork and replication fidelity. Finally we will try to obtain new crystal forms of Pol epsilon, including mutants, modified DNA substrates, and ribonucleotides and the complete four-subunit Pol epsilon (379 kDa). The proposed research will enhance our understanding of how eukaryotic cells duplicate their DNA.
Principal InvestigatorJohansson, Erik
Coordinating organisation
Umeå University
Funder
Period
2014-01-01 － 2017-12-31
National Category
Structural BiologyBiochemistry and Molecular BiologyGenetics
Identifiers
DiVA, id: project:1337Project, id: 2013-05888_VR

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Structural BiologyBiochemistry and Molecular BiologyGenetics

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