The genetic information stored in DNA is protected from attack of many chemicals by the double-stranded nature of this molecule. This protection reduces mutations and assures greater stability for the genetic material. However, copying of the genetic material requires temporary separation of the DNA strands exposing them to chemical hazards. The investigator recently used genetic method to show that the process of transcription creates C to T mutations in the non-transcribed strand of an Escherichia coli gene. The data suggested that this occurs because the rate of hydrolytic deamination of cytosines in the non-transcribed strand is higher. He proposes experiments tha will establish the biochemical basis of this phenomenon, show that it is true of other genes, and test the possibility that certain chemical mutagens may also have a similar strand bias. To accomplish this, he will reproduce the strand-specific mutations in vitro and test several predictions regarding thes mutations based on current understanding of transcription in E. coli. The results from this work should create a new perspective on the action of mutagens and provide a greater understanding of the process of transcript elongation.
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