Responses of E. coli to DNA Damage and Stress
Exposure of Escherichia coli to agents that damage DNA or interfere with DNA replication results in the induction of the SOS response. A number of chromosomal genes that are repressed by the LexA protein are transcribed at higher levels and various lysogenic bacteriophage are induced. The RecA protein becomes activated by binding to some intracellular inducing signal, probably single-stranded DNA and then mediates proteolytic cleavage of LexA and bacteriophage repressors by facilitating an otherwise latent capacity of these molecules to autodigest. The products of the SOS-regulated operon umuDC axe required for most UV and chemical mutagenesis. We have shown that the UmuD protein shares homology with the carboxyl-terminal domains of LexA and several bacteriophage repressors and is activated for its role in mutagenesis by a RecA-mediated proteolytic event. Thus the regulation of umuD involves a transcriptional derepression and a posttranslational activation that are mechanistically and evolutionary related. A set of missense mutants of umuD was isolated and shown to encode mutant UmuD proteins that are deficient in RecA-mediated cleavage in vivo but which can be partially cleaved at a higher UV dose. Most of these mutations are dominant to umuD* with respect to UV mutagenesis yet do not interfere with SOS induction. Although both UmuD and UmuD’ form homodimers, we have found evidence that they preferentially form heterodimers. These studies of umuD have suggested a role for intact UmuD in the modulation of SOS mutagenesis. Other genetic studies have indicated that the RecA protein plays a third role in mutagenesis besides mediating the cleavage of LexA and UmuD. In addition, we have observed that efficiency of UV mutagenesis is greatly reduced by mutations affecting the groESand groEL heat-shockgenes. These genes encode proteins that function as molecular chaperones which mediate protein folding and protein-protein interaction. It seems possible that they may play a role in the proper assembly of a protein complex required for SOS mutagenesis.
KeywordsChemical Mutagenesis LexA Protein Mediate Cleavage Bacteriophage Repressor Transcriptional Derepression
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