The hydantoin lesions formed from oxidation of 7,8-dihydro-8-oxoguanine are potnt sources of replication errors in vivo; Henderson, P.T.; Delaney, J.C.; Muller, J. G.; Neeley, W.L.; Tannenbaum, S.R.; Burrows, C.J.; Essigmann, J.M. Biochemistry (accelerate
Single-stranded DNA genomes have been constructed that site-specifically contain the 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) oxidation products guanidinohyndantoin (Gh), and the two stable stereoisomers of spiroiminodihydantoin (Sp1 and Sp2). The circular viral genomes were transfected into wild-type AB1157 Escherichia coli and the efficiency of lesion bypass by DNA polymerase(s) was assessed. Viral progeny were analyzed for mutation frequency and type using the recently developed restriction endonuclease and post-labeling (REAP) assay. Gh was bypassed nearly as efficiently as the parent 8-oxoG, but was highly mutagenic, causing almost exclusive G{yields}C transversions. The stereoisomers Sp1 and Sp2 were, in comparison, much stronger blocks to DNA polymerase extension, and caused a mixture of G{yields}T and G{yields}C transversions. The ratio of G{yields}T to G{yields}C mutations for each Sp lesion was dependent on the stereochemical configuration of the base. All observed mutation frequencies were at least an order of magnitude higher than those caused by 8-oxoG. Were these lesions to be formed in vivo, our data show that they are absolutely miscoding, and may be refractory to repair after translesion synthesis.
- Research Organization:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 15013805
- Report Number(s):
- UCRL-JRNL-200648; BICHAW; TRN: US200803%%787
- Journal Information:
- Biochemistry, Journal Name: Biochemistry; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
Similar Records
Substitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP and dGMP To Be Inserted opposite Guanidinohydantoin
Viewing Human DNA Polymerase β Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography