Deoxyribonucleic Acid Damage in Escherichia coli

INTRODUCTION............................................................ 61 PROCESSING OF DAMAGED DNA ............................................................ 61 SOS REGULATORY NETWORK ............................................................. 61 Present Model for SOS Regulation ............................................................ 62 SOS Responses ............................................................ 62 Development of the Model for SOS Regulation .................................. .......................... 64 Genetic studies of recA and lexA .6....................................4i................... 64 Deduction of the essential elements of SOS regulation .......................................................... 65 Identification of genes in the SOS network............ ............ 66 Biochemical studies of SOS regulation............................................................ 67 SOS-Inducing Signal ............................................................ 67 Central role of RecA activation ............................................................. 67 Agents and treatments which cause SOS induction ............................................................ 68 Indirect induction.6.............................. . . . .. . .. . .. . . 68 Role of DNA replication ............................................................ 68 Involvement of small molecules .................................... ...................... . .68 Role of single-strand DNA-binding protein ........................................................... 69 Fine Tuning in the Induction of the SOS System ........................................................... 69 Intermediate states of induction.............................................................69 Factors influencing the extent of SOS induction ............................................................ 70 Strategies for modulating individual genes within the SOS network....................................... . 70 INDUCTION OF HEAT SHOCK GENES BY DNA-DAMAGING AGENTS .................................... 71 ADAPTIVE RESPONSE TO METHYLATING AND ETHYLATING AGENTS ........... ................... 71 Biochemistry of the Adaptive Response ................. ........................................... 72 06-Alkylguanine-DNA alkyltransferase .................. ......................................... 72 3-Methyladenine-DNA glycosylase II............................................................. 72 Regulation of the Adaptive Network .............. .............................................. 72 Effect of the Adaptive Response on Mutagenesis................................ ........................... 72 Comparison of the SOS, Heat Shock, and Adaptive Regulatory Systems ............... ....................... 73 ROLE OF SOS PROCESSING IN MUTAGENESIS ............................................................ 73 Mutagenesis by UV and Most Chemicals Is Not a Passive Process ....................... ....................... 73 Weigle reactivation and Weigle mutagenesis ............................................................. 73 Bacterial mutagenesis ............................................................. 74 Significance of umuD and umuC Mutations ............................................................. 74 Isolation of umuD and umuC mutations............................................................. 75 Identification of the umuD and umuC gene products ............................................................ 75 umuD and umuC Analogs on Naturally Occurring Plasmids ...................................................... 75 pKM101 ............................................................. 75 Relationship of pKM101-mediated processes to cellular gene functions ...................................... 76 mucA and mucB genes of pKM101 are analogs of umuD and umuC ............... ......................... 76 Distribution of umuDC functions in other bacteria ............................................................. 76 A Second Requirement for the RecA Protein in Mutagenesis .................................................... 77 Effect of the recA430 mutation on mutagenesis ............................................................. 77 Evidence suggesting that UV mutagenesis does not require the induction of genes other than those repressed by LexA ..................................................... 77 Other evidence...................................77 Targeting of UV and Chemical Mutagenesis ................................ 78 Most UV and chemical mutagenesis is targeted ........................................................ ..78 Hotspots ......................................................... 78 Concept of HFOs and LFOs ......................................................... 79 (i) HFOs ......................................................... 79 (ii) LFOs ........................................................... 79 Consequences of SOS Processing of DNA Not Damaged by Exogenous Agents ........... ................... 79 Relationship of SOS processing to the spontaneous mutation frequency ............ ........................ 79 Mutagenesis of undamaged bacteriophage in SOS-induced cells which depends on SOS processing 80