Glycosylase action is followed by the endonuclease APE1, which cleaves the polynucleotide chain on the 5’ side. This in turn attracts a replication complex including the DNA polymerase d/E and ancillary components, which performs a short synthesis reaction extending for two to 10 nucleotides. The displaced material is removed by the endonuclease FEN1.

TLS Online TPP Program

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#Unit 3. Fundamental Processes

The oxoG adduct is highly mutagenic because it can base-pair with adenine as well as with cytosine. If it base-pairs with adenine during replication, it gives rise to a G:C to T:A transversion, which is one of the most common mutations found inhuman cancers.

TLS Online TPP Program

#Id: 3266

#Unit 3. Fundamental Processes

The carcinogenic effects of ionizing radiation and oxidizing agents are partly caused by free radicals that convert guanine to oxoG.

TLS Online TPP Program

#Id: 3267

#Unit 3. Fundamental Processes

Bruce Ames of the University of California at Berkeley devised a simple test for the potential carcinogenic effects of chemicals based on their capacity to cause mutations in the bacterium Salmonella typhimurium.

TLS Online TPP Program

#Id: 3268

#Unit 3. Fundamental Processes

The Ames test uses a strain of S. typhimurium that is mutant for the operon responsible for the biosynthesis of the amino acid histidine. For example, the mutant operon might contain a missense or a frameshift mutation in one of the genes for histidine biosynthesis.

TLS Online TPP Program

#Id: 3271

#Unit 3. Fundamental Processes

Chemicals that are found to be mutagenic in the Ames test can then be tested for their potential carcinogenic effects in animals.

TLS Online TPP Program

#Id: 3272

#Unit 3. Fundamental Processes

Mismatch Repair Correction of the rare mismatches left after replication in E. coli improves the overall fidelity of replication by an additional factor of 10^2 to 10^3.