Error-prone repair

Induced mutagenesis in Escherichia coli is an active process involving proteins with DNA replication, repair, and recombination functions. The available evidence suggests that mutations are generated at sites where DNA has been damaged and that they arise via an error-prone repair activity. In an attempt to understand what specific contributions to mutagenesis are made by DNA lesions, we have studied the mutational specificity of some carcinogens, such as benzo[a]pyrene and aflatoxin, whose chemical reactions with DNA are... 

The Use of the Plasmid pKMlOl. Salmonella typhimurium LT2 strains do not appear to possess classical error-prone repair as found in E. coli strains and some other members of the Enterobacteria (Walker, 1984 Sedgwick and Goodwin, 1985). This is due to a deficiency in umu D activity in these Salmonella strains (Herrera et... 

Encodes protein that inhibits cell division, possibly to allow time for DNA repair Encodes RecA protein, required for error-prone repair and recombinational repair Encodes DNA polymerase IV... 

Goodman, M.F. (2002) Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu. Rev. Biochem. 71, 17-50. Review of a class of DNA polymerases that continues to grow. 

As with photoreactivation, excision repair and recombination repair, the story starts with yet another form of reactivation of UV-irradiated phage in host cells. This phenomenon was first observed by Luria(1947), but came to be known as Weigle reactivation. He observed that UV-irradiated bacteriophageX survives better when plaqued on E. coli which has been previously irradiated with a small dose of UV (Weigle, 1953). This paper also showed that whatever repair process is induced in the host cells by these small doses of UV was mutagenic. For a time it came to be known as error-prone repair, distinguishing it from excision repair which was said to be error-free. The distinction was dramatically demonstrated by Howard-Flanders, who found that the rate of induction of mutation by UV was 100-1000-fold higher in strains of E. coli defective in excision repair. 

Error prone repair or no repair followed by cell replication... 

This test has several advantages in that primary liver cells have considerable activation capacity and the test measures an event at the DNA level. It does not, however, distinguish between error-free repair and error-prone repair, the latter being itself a mutagenic process. Thus it cannot distinguish between events that might lead to toxic sequelae and those that do not. A modification of this test measures in vivo unscheduled DNA synthesis. In this modification animals are first treated in vivo, and primary hepatocytes are then prepared and treated as already described. 

D. Chakravarti, P. C. Mailander, K.-M. Li, S. Higginbotham, and H. L. Zhang, Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene. Oncogene 20 (2001), 7945-7953. 

As described above, activation of the editing system stalls replication at a thymine dimer. In SOS repair, the editing system is relaxed to allow polymerization to proceed across a dimer. Relaxation of the editing system means a loss of the ability to remove incorrect bases added to the growing strand. Most of the time, pol III inserts two adenines at a dimer site. However, the distortion increases the error frequency, allowing other nucleotides to be added to the chain. This error-prone repair is the major cause of UV-induced mutagenesis. 

A pair of bacterial genes, called umuC and umuD have been implicated in error prone repair. After expression of the two genes, the umuD gene product undergoes proteolytic cleavage to give the UmuD protein. Two of these combine with UmuC (the protein product of umuC) to yield trimeric UmuD 2C. This trimeric complex may be the error prone polymerase. 

Error-Prone Repair and the SOS Response Mismatch Repair (Figure 25.16)... 

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