SOS Regulon

cI Inactivation - In order for phage to convert from lysogeny to lytic growth, the cI repressor must be inactivated. Under conditions of DNA damage, the cI repressor is inactivated by proteolytic cleavage of the E. coli SOS system, one of the elements in error-prone DNA repair, in which the genes are controlled by a single repressor-operator system. Such a set of unlinked genes, regulated by a common mechanism, is called a regulon.

SOS regulon controls - The control elements in the E. coli SOS regulon are the products of genes lexA and recA. RecA protein stimulates DNA strand pairing during recombination. Remarkably, this small protein has an enzymatic activity in addition to the activities involved in recombination. When bound to single-strand DNA, RecA can stimulate proteolytic cleavage of the proteins encoded by cI, lexA, and umuD. LexA is a repressor that binds to at least 15 different operators scattered about the E. coli genome (Figure 26.32). Each operator controls the transcription of one or more proteins that help the cell respond after environmental damage that might harm the genetic apparatus. These proteins include the gene products of uvrA and uvrB, involved in nucleotide excision repair; umuC,D, involved in error-prone mutagenesis; sulA, involved in cell division control; dnaA, the structural gene for DNA polymerase II; recA itself; lexA itself; and several genes of unknown function, including dinA, dinB, and dinF.

Single-strand DNA trigger - In a healthy cell, lexA and recA are expressed at low levels, with sufficient LexA protein to turn off the synthesis of the other SOS genes completely. LexA protein does not completely abolish the transcription of either lexA or recA. The trigger that activates the SOS system after damage is thought to be single-strand DNA. UV irradiation and other conditions generate gapped DNA structures that induce the SOS system. RecA binding within a gap activates proteolysis by a mechanism not yet clear. Intracellular levels of LexA decrease, removing the LexA barrier to recA transcription. RecA protein accumulates in large amounts. Cleavage of the LexA protein activates transcription of all genes under lexA control. In a lysogen, cleavage of cI repressor is stimulated, as well, activating prophage excision and replication.

Sequence Similarities - DNA sequence analysis of operators that respond to LexA has yielded a consensus sequence, with 7 highly conserved bases in a 20-base-pair region. Different LexA-sensitive genes have this sequence located quite differently with respect to the transcriptional start site. Therefore, it appears that the exact location of bound repressor is not critical to ensure that transcription will be inhibited.

See also: SOS Response (from Chapter 25)

INTERNET LINK: Regulon DB, A Database of Transcriptional Regulation in E. coli