Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta.
The Saccharomyces cerevisiae RAD30 gene functions in error-free replication of UV-damaged DNA. RAD30 encodes a DNA polymerase, Pol eta, which inserts two adenines opposite the two thymines of a cis-syn thymine-thymine (T-T) dimer. Here we use steady-state kinetics to determine the accuracy of DNA synthesis opposite the T-T dimer. Surprisingly, the accuracy of DNA synthesis opposite the damaged DNA is nearly indistinguishable from that opposite nondamaged DNA, with frequencies of misincorporation of about 10(-2) to 10(-3). These studies support the hypothesis that unlike most DNA polymerases, Pol eta is able to tolerate distortions in DNA resulting from damage, which then enables the polymerase to utilize the intrinsic base pairing ability of the T-T dimer.
Washington
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Sealy Center for Molecular Science, University of Texas Medical Branch, 6.104 Medical Research Building, 11th & Mechanic Streets, Galveston, TX 77555-1061, USA.
Johnson
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Prakash
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Prakash
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D001483:Base Sequence; D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D019281:Dimerization; D013698:Templates, Genetic; D013941:Thymine / Q000378:metabolism*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase; D013941:Thymine; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases