PMID:11734560
| Citation |
Shen, X, Sayer, JM, Kroth, H, Ponten, I, O'Donnell, M, Woodgate, R, Jerina, DM and Goodman, MF (2002) Efficiency and accuracy of SOS-induced DNA polymerases replicating benzo[a]pyrene-7,8-diol 9,10-epoxide A and G adducts. J. Biol. Chem. 277:5265-74 |
|---|---|
| Abstract |
Nucleotide incorporation fidelity, mismatch extension, and translesion DNA synthesis efficiencies were determined using SOS-induced Escherichia coli DNA polymerases (pol) II, IV, and V to copy 10R and 10S isomers of trans-opened benzo[a]pyrene-7,8-diol 9,10-epoxide (BaP DE) A and G adducts. A-BaP DE adducts were bypassed by pol V with moderate accuracy and considerably higher efficiency than by pol II or IV. Error-prone pol V copied G-BaP DE-adducted DNA poorly, forming A*G-BaP DE-S and -R mismatches over C*G-BaP DE-S and -R correct matches by factors of approximately 350- and 130-fold, respectively, even favoring G*G-BaP DE mismatches over correct matches by factors of 2-4-fold. In contrast, pol IV bypassed G-BaP DE adducts with the highest efficiency and fidelity, making misincorporations with a frequency of 10(-2) to 10(-4) depending on sequence context. G-BaP DE-S-adducted M13 DNA yielded 4-fold fewer plaques when transfected into SOS-induced DeltadinB (pol IV-deficient) mutant cells compared with the isogenic wild-type E. coli strain, consistent with the in vitro data showing that pol IV was most effective by far at copying the G-BaP DE-S adduct. SOS polymerases are adept at copying a variety of lesions, but the relative contribution of each SOS polymerase to copying damaged DNA appears to be determined by the lesion's identity. |
| Links |
PubMed Online version:10.1074/jbc.M109575200 |
| Keywords |
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/chemistry; Base Pair Mismatch; DNA Adducts/genetics; DNA Repair; DNA-Directed DNA Polymerase/chemistry; DNA-Directed DNA Polymerase/metabolism; Kinetics; Models, Chemical; Mutagens; Mutation; SOS Response (Genetics); Transfection |
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