DNA sequence analysis of spontaneous histidine mutations in a polA1 strain of Escherichia coli K12 suggests a specific role of the GTGG sequence.
Spontaneously arising histidine mutations in an Escherichia coli K12 strain deficient for DNA polymerase I were analysed at the DNA sequence level. We screened approximately 150,000 colonies and isolated 106 histidine auxotrophs. Of these, 98 were unstable hisC mutations; 12 representative mutants analysed were shown to have arisen by the excision of a single quadruplet repeat in the sequence 5'-GCTGGCTGGCTGGCTG-3'. Of the eight mutations at other sites, three hisA deletions and one hisD deletion occurred as a consequence of misalignment of tandemly repeated pentamers (hisD) or decamers (hisA). A single hisA point mutation was found to be a missense mutation. Two extended deletions, covering the his operon were not analysed. We could not identify the hisC deletion by sequencing. We conclude that polA1 is a strong mutator that induces mutations mostly of the minus frameshift and deletion type by a Streisinger-type of mispairing in repetitive DNA sequences. Finally, the possible role of a 5'-GTGG-3' sequence and its inverted or direct complements, which are found in the vicinity of all the deletions and frameshifts, is discussed.
Jankovic
M
M
Institute of Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia.
Kostic
T
T
Savic
D J
DJ
D001483:Base Sequence; D004256:DNA Polymerase I / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D006639:Histidine / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D012091:Repetitive Sequences, Nucleic Acid
D004269:DNA, Bacterial; D006639:Histidine; D004256:DNA Polymerase I