Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli

Abstract

UV induced mutations in E. coli and some of its phages are caused primarily by inaccurate repair of UV damaged DNA. Most of the UV damage produced in the DNA of surviving bacteria is repaired by relatively 'error proof' mechanisms (e.g., photoreactivation, 'short patch' excision repair, the major pathways of recombinational postreplication repair), which do not contribute substantially to UV mutagenesis. Some kinds of DNA damage (probably single strand gaps not repairable by any constitutive accurate mechanism) are targets for the activity of inducible 'error prone' repair activity ('SOS' repair), which is entirely responsible for UV mutagenesis in E. coli and in λ bacteriophage. SOS repair may participate in two minor DNA repair pathways: a 'long patch' excision repair and chloramphenicol sensitive postreplication repair. SOS repair activity is repressed in undamaged wild type cells, but is induced in response to UV radiation and other agents (including many mutagens and carcinogens) that damage DNA or interrupt its replication. Such treatments generate a regulatory signal (the 'SOS' signal), which initiates a complex induction process culminating in the derepression of a group of metabolically diverse but coordinately regulated functions ('SOS' functions), all of which presumably promote the survival of the damaged cell or that of its phages. At least one kind of SOS repair activity induced in E. coli has been identified as a DNA polymerizing activity that is distinguishable from the activities of the constitutive DNA polymerases I, II, and III by its ability to polymerize DNA past pyrimidine dimers in the template strand, with a high probability of error. UV mutagenesis in E. coli and λ bacteriophage may be due primarily to the insertion of 'wrong' bases by this UV inducible SOS repair activity as it replicates DNA past noninstructive UV photoproducts, which are not necessarily pyrimidine dimers. The inducible component of this SOS repair system need not be a new DNA polymerase, but may be a factor that inhibits the 3' 5' exonuclease 'proofreading' activity of one or more of the constitutive DNA polymerases, or one that relaxes their template dependence in some other way. The kinetics of induction and decay of SOS repair activity are similar, whether the error prone activity is assayed by its capacity to enhance bacterial UV mutagenesis or to promote λ UV mutagenesis in UV irradiated hosts. In both types of assay, the half life of SOS repair activity is about 30 min. These observations are consistent with the possibility that the same inducible error prone DNA polymerase activity is responsible for both bacterial and phage UV mutagenesis. There is some evidence that mutagens and carcinogens induce DNA repair activities in mammalian cells. It is not known whether these activities are error prone or whether they are induced in coordination with other SOS like functions in response to DNA damage. If so, at least two such functions (induction of latent virus and of error prone DNA repair activity) could contribute to carcinogenesis.