In most higher organisms, DNA is modified after synthesis by the enzymatic conversion of many cytosine residues to 5-methylcytosine. For several years, control of gene activity by DNA methylation has been recognized as a logically attractive possibility, but experimental support has proved elusive. However, there is now reason to believe, from recent studies, that DNA methylation is a key element in the hierarchy of control mechanisms that govern vertebrate gene function and differentiation.

https://science.sciencemag.org/content/sci/210/4470/604.full.pdf

DNA methylation and gene function

https://mmbr.asm.org/content/mmbr/48/1/60.full.pdf

Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli.

INTRODUCTION .............................................................. 869 Enzymatic Repair of UV Damage in E. coli ......... .......................... 869 Error-Proof and Error-Prone Pathways of DNA Repair ....... ................. 871 The \"SOS\" Hypothesis: the Regulatory Role of DNA Damage ...... ............ 874 EVIDENCE FOR THE INDUCIBILITY OF ERROR-PRONE REPAIR (\"SOS REPAIR\") ACTIVITY ..................................................... 875 SOS Repair of Bacteriophage DNA ............ ............................... 875 SOS Repair of Bacterial DNA ................ ................................ 876 Evidence from studies of repair-deficient mutants ....... .................... 876 Evidence from studies of postreplication repair ........ ...................... 879 MANIFESTATIONS OF SOS REPAIR AND THEIR SIGNIFICANCE ..... ...... 879 Mutation Frequency Response to Increasing Fluence of UV Radiation ..... ..... 879 The UV Lesion Responsible for Induction of SOS Functions.................... 880 Kinetics of Induction and Decay of SOS Repair Activity ....... ................ 882 Time of Action of SOS Repair in UV Mutagenesis ...... ........................ 882 Cryptic Premutational Lesions Susceptible to SOS Repair ...................... 884 Mutator Effect of SOS Repair on Undamaged DNA ....... ..................... 885 PLASMIDS AND SOS REPAIR ................................................ 886 MECHANISM OF SOS REPAIR ............................................... 886 Mechanism of SOS Repair in Bacteriophage ......... .......................... 886 Mechanism of SOS Repair in Bacteria ........... ............................. 887 IMPLICATIONS OF SOS REPAIR FOR CARCINOGENESIS ................... 888 REGULATION OF SOS REPAIR AND OTHER UV-INDUCIBLE FUNCTIONS . 889 PROTEASES AND THE EXPRESSION OF SOS FUNCTIONS .................. 894 CONCLUSIONS ............................................................... 895 APPENDIX................................................................... 896 LITERATURE CITED ......................................................... 898

Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli.

The induction of sister chromatid exchanges (SCE) was examined in Chinese hamster ovary cells irradiated in the G1 phase of the cell cycle with alpha-particles from a plutonium-238 source. A significant increase in the frequency of SCE occurred with doses as low as 0.31 mGy (31 millirads). Although 30% of the cells showed an increased frequency of SCE at this dose, less than 1% of cell nuclei were actually traversed by an alpha-particle. A dose of approximately 2.0 Gy was necessary to produce a similar increase in SCE by X-rays. These results indicate that genetic damage may be induced by low doses of alpha-radiation in cell nuclei not actually traversed by an alpha-particle. This phenomenon may have important implications in the estimation of risks of such exposures.

https://cancerres.aacrjournals.org/content/canres/52/22/6394.full.pdf

Induction of sister chromatid exchanges by extremely low doses of alpha-particles.

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . ... . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . 229 LONG-PATCH MISMATCH CORRECTION . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . 231 Specificity of Methyl-Directed Mismatch Repair in E. coli.. . ...... . . . ..... . .. . .... . . . . . . 231 Initiation of the Methyl-Directed Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 The Excision Reaction in Methyl-Directed Repair . . . . . . . . .... . . . . . . . . . . . . . . . . . . . ... . . . . 235 Methyl-Directed Repair and Replication Fidelity . . . . ....... . . ..... . . . . . . . . . . . . . . . . .. . 238 mutHLSU Gene Products and the Recombination Heteroduplex..... . . . . . . . . . . . . . . . . . . 239 Long-Patch. Strand-Specific Mismatch Repair in Eukaryotic Cells . . . . . .. .. . . . . . . . . . . . . 241 SHORT-PATCH MISMATCH REPAIR. . . . . . . . . . . . . . . . . . . . . . . ... ....... ......... 243 VSP Mismatch Correction in E. coli 243 MutY-Dependent G-A->G'C Mismatch Repair in E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 244 ReeF-Dependent Resolution of Heteroduplex DNA in E. coli ... . .. . . . . . .. . . . . . ........ 246 G-T->G' C Short-Patch Repair in Mammalian Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

Mechanisms and biological effects of mismatch repair.

Ultraviolet reactivation and ultraviolet mutagenesis of λ in different genetic systems

12-O-Tetradecanoylphorbol 13-acetate (TPA), a powerful tumor promoter, is shown to induce sister chromatid exchanges (SCEs), whereas the nonpromoting derivative 4-O-methyl-TPA does not. Inhibitors of tumor promotion--antipain, leupeptin, and fluocinolone acetonide--inhibit formation of such TPA-induced SCEs. TPA is a unique agent in its induction of SCEs in the absence of DNA damage, chromosome aberrations, mutagenesis, or significant toxicity. Because TPA is known to induce several gene functions, we speculate that it might also induce enzymes involved in genetic recombination. Thus, the irreversible step in tumor promotion might be the result of an aberrant mitotic segregation event leading to the expression of carcinogen/mutagen-induced recessive genetic or epigenetic chromosomal changes.

Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis

E. coli strains carrying the dam-3 and dam-4 mutations resulting in reduced levels of 6-methyladenine in the DNA have been found to be more sensitive to base analogue mutagenesis than dam
+ strains. Mutagenesis by EMS was also found to be enhanced in dam
− strains. Dam
− mutants however were not found to be hypermutable by UV light. It is concluded that the dam
− strains are deficient in the correct repair of mispairing lesions. The data are consistent with the hypothesis that 6-methyladenine residues in the DNA are involved in strand discrimination during mismatch correction.

Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance.

Replicational Fidelity: Mechanisms of Mutation Avoidance and Mutation Fixation

1,N6-Ethenoadenine (epsilon A) and 3,N4-ethenocytosine (epsilon C) are formed when electrophilic vinyl chloride (VC) metabolites, chloroethylene oxide (CEO) or chloroacetaldehyde (CAA) react with adenine and cytosine residues in DNA. They were assayed for their miscoding properties in an in vitro system using Escherichia coli DNA polymerase I and synthetic templates prepared by reaction of poly(dA) and poly(dC) with increasing concentrations of CEO or CAA. Following the introduction of etheno groups, an increasing inhibition of DNA synthesis was observed. dGMP was misincorporated on CAA- or CEO-treated poly(dA) templates and dTMP was misincorporated on CAA- or CEO-treated poly(dC) templates, suggesting that epsilon A and epsilon C may miscode. The error rates augmented with the extent of reaction of CEO or CAA with the templates. Base-pairing models are proposed for the epsilon A.G. and epsilon C.T pairs. The potentially miscoding properties of epsilon A and epsilon C may explain why metabolically-activated VC and its reactive metabolites specifically induce base-pair substitution mutations in Salmonella typhimurium. Promutagenic lesions may represent one of the initial steps in VC- or CEO-induced carcinogenesis.

/pdf/studies-on-the-miscoding-properties-of-1-n6-ethenoadenine-30i3876hqr.pdf

Studies on the miscoding properties of 1,N6-ethenoadenine and 3,N4-ethenocytosine, DNA reaction products of vinyl chloride metabolites, during in vitro DNA synthesis

Miroslaw Radman

Papers

Ultraviolet reactivation and ultraviolet mutagenesis of λ in different genetic systems

Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis

Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance.

Replicational Fidelity: Mechanisms of Mutation Avoidance and Mutation Fixation

Studies on the miscoding properties of 1,N6-ethenoadenine and 3,N4-ethenocytosine, DNA reaction products of vinyl chloride metabolites, during in vitro DNA synthesis