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COMPLEX FRAMESHIFT MUTATIONS MEDIATED BY PLASMID PKM101: MUTATIONAL MECHANISMS DEDUCED FROM 4-AMINOBIPHENYL-INDUCED MUTATION SPECTRA IN SALMONELLA
Citation:
Levine, J., R. Schaaper, AND D.M. DeMarini. COMPLEX FRAMESHIFT MUTATIONS MEDIATED BY PLASMID PKM101: MUTATIONAL MECHANISMS DEDUCED FROM 4-AMINOBIPHENYL-INDUCED MUTATION SPECTRA IN SALMONELLA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/407 (NTIS PB95125399).
Description:
We used colony probe hybridization and PCR/DNA sequencing to determine the mutations -aminobiphenyl (4-AB) +S9-induced revertants of the -1 frameshift allele in 2,300 4-aminobiphenyl of the base-substitution allele hisD3052 in strains TA1978, TA1538, and TA98 and were at strains UTH8414 and TA100 of Salmonella typhimurium. ost of the mutations sites containing guanine, which se at which 4-AB forms DNA adducts. mong revertants of the frameshift allele, a hotspot mutation involving the deletion.of a CG or GC within the sequence CGCGCGCG accounted for essentially 100% of the reversion events at the hisD3052 allele in strain TA1978 (wild type) and strain TA1538 (uvrB). n strain TA98 uvrb, pKM101), 85% of the reversion events were also this deletion; however, the remaining 15% consisted of two types of mutations: (1) complex frameshifts that can be described as a -2 or +1 frameshift and an associated base substitution and (2) 2-base deletions of the CC or GG sequences that flank the hotspot site. 4-AB reverted the base-substitution allele hisG46 only in the presence of pKM101, producing primarily (78-86%) C to A transversions. e propose a misincorporation/slippage model 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 ol the adduct leads to strand slippage in a run of repeated bases adjacent to the adducted guanine, and (3) replication of the nonadducted strand produces a frameshift associated with a base substitution.