SOS response

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The SOS response is a postreplication DNA repair system that allows DNA replication to bypass lesions or errors in the DNA. The SOS uses the RecA protein. The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the LexA repressor thereby inducing the response. It is an error prone repair system.

Mechanism

During normal growth, the SOS genes are negatively regulated by LexA repressor protein dimers. Under normal conditions, LexA binds to a 20-bp consensus sequence (the SOS box) in the operator region for those genes. Some of these SOS genes are expressed at certain levels even in the repressed state, according to the affinity of LexA for their SOS box. Activation of the SOS genes occurs after DNA damage by the accumulation of single stranded (ssDNA) regions generated at replication forks, where DNA polymerase is blocked. RecA forms a filament around these ssDNA regions in an ATP-dependent fashion, and becomes activated. The activated form of RecA acts as a coprotease in the autocatalytic digestion of the LexA repressor protein.

Once the pool of LexA decreases, repression of the SOS genes goes down according to the level of LexA affinity for the SOS boxes. Operators that bind LexA weakly are the first to be fully expressed. In this way LexA can sequentially activate different mechanisms of repair. Genes having a weak SOS box (such as lexA, recA, uvrA, uvrB, and uvrD) are fully induced in response to even weak SOS-inducing treatments. Thus the first SOS repair mechanism to be induced is nucleotide excision repair (NER), whose aim is to fix DNA damage without commitment to a full-fledged SOS response.

If, however, NER does not suffice to fix the damage, the LexA concentration is further reduced, so the expression of genes with stronger LexA boxes (such as sulA, umuD, umuC - these are expressed late) is induced. SulA stops cell division by binding to FtsZ, the initiating protein in this process. This causes filamentation, and the induction of UmuDC-dependent mutagenic repair. As a result of these properties, some genes may be partially induced in response to even endogenous levels of DNA damage, while other genes appear to be induced only when high or persistent DNA damage is present in the cell.

Discovery

The SOS response was discovered and named by Miroslav Radman in 1974.[1]

Antibiotic Resistance

Recent research has shown that the SOS pathway may be essential in the acquisition of bacterial mutations which lead to antibiotic resistance.[2] Researchers are now targeting these proteins with the hopes of creating drugs that prevent SOS repair which may increase the efficacy of antibiotics.[3]

Links

The SOS Response of Escherichia coli: http://www.utoronto.ca/medicalgenetics/student%20site/undergraduate/MGY/WalkerSOS.pdf

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References

  1. Radman, M. 1974. Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis, p. 128-142. In L. Prokash, F. Sherman, M. Miller, C. Lawrence, and H. W. Tabor (ed.), Molecular and environmental aspects of mutagenesis. Charles C Thomas Publisher, Springfield, Ill
  2. Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance Ryan T. Cirz, Jodie K. Chin, David R. Andes, Valérie de Crécy-Lagard, William A. Craig, Floyd E. Romesberg Plos Biology Volume 3, Issue 6, June 2005.[1]
  3. A Molecular Target for Suppression of the Evolution of Antibiotic Resistance: Inhibition of the Escherichia coli RecA Protein by N6-(1-Naphthyl)-ADP Andrew M. Lee, Christian T. Ross, Bu-Bing Zeng, and Scott F. Singleton. J. Med. Chem., 48 (17), 5408 -5411, 2005. [2]

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