SPECTRA OF SPONTANEOUS FRAMESHIFT MUTATIONS AT THE HISD3052 ALLELE OFSALMONELLA-TYPHIMURIUM IN 4 DNA-REPAIR BACKGROUNDS

To characterize the hisD3052-1 frameshift allele of Salmonella typhimu rium, we analyzed similar to 6000 spontaneous revertants (rev) for a 2 -base deletion hotspot within the sequence (CG)(4), and we sequenced s imilar to 500 nonhotspot rev. The reversion target is a minimum of 76 bases (nucleotides 843-918) that code for amino acids within a noncons erved region of the histidinol dehydrogenase protein. Only 0.4-3.9% we re true rev. Of the following classes, 182 unique second-site mutation s were identified: hotspot, complex frameshifts requiring Delta uvrB pKM101 (TA98-specific) or not (concerted), I-base insertions, duplica tions, and nonhotspot deletions. The percentages of hotspot mutations were 13.8% in TA1978 (wild type), 24.5% in UTH8413 (pKM101), 31.6% in TA1538 (Delta uvrB), and 41.0% in TA98 (Delta uvrB, pKM101). The Delta uvrB allele decreased by three times the mutant frequency (MF, rev/10 (8) survivors) of duplications and increased by about two times the MF of deletions. Separately, the Delta uvrB allele or pKM101 plasmid inc reased by two to three times the MF of hotspot mutations; combined, th ey increased this IMF by five times. The percentage of 1-base insertio ns was not influenced by either Delta uvrB or pKM101. Hotspot deletion s and TA98-specific complex frameshifts are inducible by some mutagens ; concerted complex frameshifts and 1-base insertions are not; and the re is little evidence for mutagen-induced duplications and nonhotspot deletions. Except for the base substitutions in TA98-specific complex frameshifts, all spontaneous mutations of the hisD3052 allele are like ly templated. The mechanisms may involve (I) the potential of direct a nd inverted repeats to undergo slippage and misalignment and to form q uasi-palindromes and (2) the interaction of these sequences with DNA r eplication and repair proteins.