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- W2155488701 abstract "Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity." @default.
- W2155488701 created "2016-06-24" @default.
- W2155488701 creator A5025264975 @default.
- W2155488701 creator A5032157241 @default.
- W2155488701 date "2009-05-14" @default.
- W2155488701 modified "2023-09-26" @default.
- W2155488701 title "Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase ι" @default.
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- W2155488701 doi "https://doi.org/10.1038/emboj.2009.122" @default.
- W2155488701 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2693154" @default.
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- W2155488701 hasPublicationYear "2009" @default.
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