Translesion DNA synthesis by yeast DNA polymerase eta on templates containing N2-guanine adducts of 1,3-butadiene metabolites

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

doi:10.1074/jbc.M007867200

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Translesion DNA synthesis by yeast DNA polymerase eta on templates containing N2-guanine adducts of 1,3-butadiene metabolites

Journal article

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Translesion DNA synthesis by yeast DNA polymerase eta on templates containing N2-guanine adducts of 1,3-butadiene metabolites

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

The Journal of biological chemistry, Vol.276(4), pp.2517-2522

01/26/2001

DOI: 10.1074/jbc.M007867200

PMID: 11062246

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Abstract

Yeast DNA polymerase eta 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 N(2)-guanine adducts of stereoisomeric 1,3-butadiene metabolites. Here we showed that yeast polymerase eta replicates DNA containing the monoadducts (S)-butadiene monoepoxide and (S,S)-butadiene diolepoxide N(2)-guanines albeit at an approximately 200-300-fold lower efficiency relative to the control guanine. Interestingly, nucleotide incorporation opposite the (R)-butadiene monoepoxide and the (R,R)-butadiene diolepoxide N(2)-guanines was approximately 10-fold less efficient than incorporation opposite their S stereoisomers. Polymerase eta 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 eta does not bypass the (R,R)- and (S,S)-butadiene diolepoxide N(2)-guanine-N(2)-guanine intra- strand cross-links, and replication is completely blocked just prior to the lesion. Collectively, these data suggest that polymerase eta can tolerate the geometric distortions in DNA conferred by the N(2)-guanine butadiene monoadducts but not the intrastrand cross-links.

DNA Replication

Epoxy Compounds - metabolism

Guanine - analogs & derivatives

Stereoisomerism

Butadienes - metabolism

Saccharomyces cerevisiae - enzymology

DNA-Directed DNA Polymerase - metabolism

Glycols - metabolism

Carcinogens - metabolism

DNA Adducts - metabolism

Details

Title: Subtitle: Translesion DNA synthesis by yeast DNA polymerase eta on templates containing N2-guanine adducts of 1,3-butadiene metabolites
Creators: Irina G Minko - Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1071, USA
M Todd Washington
Louise Prakash
Satya Prakash
R. Stephen Lloyd
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.276(4), pp.2517-2522
DOI: 10.1074/jbc.M007867200
PMID: 11062246
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: GM19261 / NIGMS NIH HHS ES06676 / NIEHS NIH HHS S11-ES10018 / NIEHS NIH HHS ES05355 / NIEHS NIH HHS
Language: English
Date published: 01/26/2001
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984025276502771

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