DNA Sequence Analysis of Spontaneous Histidine Mutations in a polA1 Strain of Escherichia Coli K12 Suggests a Specific Role of the GTGG Sequence

Mol Gen Genet. 1990 Sep;223(3):481-6. doi: 10.1007/BF00264457.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA Polymerase I / genetics*
  • DNA Polymerase I / metabolism
  • DNA, Bacterial / genetics
  • Escherichia coli / genetics*
  • Histidine / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation*
  • Operon
  • Repetitive Sequences, Nucleic Acid

Substances

  • DNA, Bacterial
  • Histidine
  • DNA Polymerase I