Mutagenesis

Abstract

Mutations have a potential for either positive or negative effects on an organism. To combat the deleterious effects of excessive mutagenesis, elaborate systems of enzymes have evolved to correct errors that arise spontaneously in cells or induced following DNA damage. However, DNA must necessarily change as organisms evolve, thus, some low level of mutagenesis is tolerated perhaps even promoted to assure normal and healthy levels of genetic variation of populations.

Keywords: DNA replication; DNA repair; evolution; genotoxicity; carcinogenesis

Figure 1.

Proofreading activity of DNA polymerase. Following an incorrect insertion of a nucleotide (‘Error’), DNA pol stops, reverses direction (3′→5′) and removes a portion of the nascent strand (top blue strand) that includes the error as well as some of the surrounding nucleotides. Following removal of sequences, synthesis of the nascent strand resumes.

Figure 2.

Shuttle vector system. A hypothetical representation of a shuttle vector plasmid map and general approach used to detect mutations that arise in mammalian cells. Shuttle vectors can comprise of several segments, including a mutagenic target sequence (red), sequences for selection and replication in Escherichia coli (blue) and sequence for replication in a mammalian cell line. The vector can be introduced into the appropriate mammalian host and then exposed to the mutagenic treatment of interest (e.g. ultraviolet). The vector DNA is retrieved from a cell line, then introduced into the appropriate E. coli strain (‘tester strain’) for rapid detection of mutations in the bacterial target sequence (e.g. lacI).

Figure 3.

Model for SOS mutagenesis. Replication is blocked when the bacterial DNA pol III encounters and stalls at a bulky lesion such as ultraviolet‐induced cyclobutane pyrimidine dimers. Shown here is a C‐T dimer. Following the induction of the SOS response the levels of RecA, UmuC and UmuD′ proteins increase and assemble at the lesion. This assembled complex (‘mutasome’) is thought to direct DNA pol III to synthesize past the lesion, possibly inserting an incorrect base in the nascent strand.

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References

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How to Cite close
Ennis, Don G(Apr 2001) Mutagenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000559]