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RECORD NUMBER: 2 OF 7

OLS Field Name OLS Field Data
Main Title Complex Frameshift Mutations Mediated by Plasmid pKM101: Mutational Mechanisms Deduced from 4-Aminobiphenyl-Induced Mutation Spectra in Salmonella.
Author Levine, J. G. ; Schaaper, R. M. ; DeMarini., D. M. ;
CORP Author Environmental Protection Agency, Research Triangle Park, NC. Genetics Toxicology Div. ;North Carolina Univ. at Chapel Hill. Dept. of Environmental Sciences and Engineering. ;National Inst. of Environmental Health Sciences, Research Triangle Park, NC. Lab. of Molecular Genetics.
Publisher c1994
Year Published 1994
Report Number EPA/600/J-94/407;
Stock Number PB95-125399
Additional Subjects Frameshift mutation ; Plasmids ; Salmonella ; Mutagens ; Alleles ; Base sequence ; DNA repair ; SOS response(Genetics) ; Polymerase chain reaction ; Dose-response relationships ; Reprints ; 4-aminobiphenyl
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Status
NTIS  PB95-125399 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. 03/06/1995
Collation 20p
Abstract
The authors used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 2,400 4-aminobiphenyl (4-AB) + S9-induced revertants of the -1 frameshift allele hisD3052 and of the base-substitution allele hisG46 of Salmonella typhimurium. Most of the mutations occurred at sites containing guanine, which is the primary base at which 4-AB forms DNA adducts. A hotspot mutation involving the deletion of a CG or GC within the sequence CGCGCGCG accounted for 100 and 99.9%, respectively, of the reversion events at the hisD3052 allele in the pKM101 plasmid-minus strains TA1978 (uvr(+)) and TA1538 (Delta uvrB). In strain TA98 (DeltauvrB, pKM101), which contained the SOS DNA repair system provided by the pKM101 plasmid, approximately 85% of the revertants also contained the hotspot deletion; the remaining approximately 15% contained one of two types of mutations: (1) complex frameshifts that can be described as a -2 or +1 frameshift and an associated based substitution and (2) deletions of the CC or GG sequences that flank the hotspot site (CCGCGCGCGG). The authors propose a misincorporation/slippage model to account for these mutations in which (1) pKM101-mediated misincorporation and translesion synthesis occurs across a 4-AB-adducted guanine; (2) the instability of such a mispairing and/or the presence of the adduct leads to strand slippage in a run of repeated bases adjacent to the adducted guanine; and (3) continued DNA synthesis from the slipped intermediate produces a frameshift associated with a base substitution. (Copyright (c) 1994 by the Genetics Society of America.)