Translesion DNA Synthesis by Yeast DNA Polymerase η on Templates Containing N2-Guanine Adducts of 1,3-Butadiene Metabolites

Irina G. Minko, M. Todd Washington, Louise Prakash, Satya Prakash, R. Stephen Lloyd

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Yeast DNA polymerase η can replicate through cis-syn cyclobutane pyrimidine dimers and 8-oxoguanine lesions with the same efficiency and accuracy as replication of an undamaged template. Previously, it has been shown that Escherichia coli DNA polymerases I, II, and III are incapable of bypassing DNA substrates containing N2-guanine adducts of stereoisomeric 1,3-butadiene metabolites. Here we showed that yeast polymerase η replicates DNA containing the monoadducts (S)-butadiene monoepoxide and (S,S)-butadiene diolepoxide N2-guanines albeit at an ∼200-300-fold lower efficiency relative to the control guanine. Interestingly, nucleotide incorporation opposite the (R)-butadiene monoepoxide and the (R,R)-butadiene diolepoxide N2-guanines was ∼10-fold less efficient than incorporation opposite their S stereoisomers. Polymerase η preferentially incorporates the correct nucleotide opposite and downstream of all four adducts, except that it shows high misincorporation frequencies for elongation of C paired with (R)-butadiene monoepoxide N 2-guanine. Additionally, polymerase η does not bypass the (R,R)- and (S,S)-butadiene diolepoxide N2-guanine-N2-guanine intra-strand cross-links, and replication is completely blocked just prior to the lesion. Collectively, these data suggest that polymerase η can tolerate the geometric distortions in DNA conferred by the N2-guanine butadiene monoadducts but not the intrastrand cross-links.

Original languageEnglish (US)
Pages (from-to)2517-2522
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number4
DOIs
StatePublished - Jan 26 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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