prokaryotic (SOS) response

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DESCRIPTION:

Ultraviolet light damages the DNA of cells, which prevents duplication and thereby cell division. Bacteria respond to such damage by producing a number of proteins that help to detect, bypass, and repair the damage. This SOS response system displays intricate dynamical behavior—in particular the tightly regulated turn-on and turn-off of error-prone DNA polymerases that result in mutagenesis—and the puzzling resurgence of SOS gene activity 30–40 min after irradiation.
The SOS response in the bacterium E. coli encompasses many proteins involved in detecting and repairing DNA damaged by a variety of agents, such as UV radiation, or chemicals such as mitomycin and bleomycin. A complex regulatory network, comprising both transcriptional and post-translational regulators, controls the concentrations and levels of activity of these proteins.

The collective actions of this regulatory network are orchestrated so that the SOS response is commensurate with the magnitude of DNA damage. The prokaryotic SOS system is regulated by two key proteins: LexA and RecA. The LexA homodimer is a transcriptional repressor that binds to operator sequences commonly referred to as SOS boxes. In Escherichia coli it is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes.
Briefly, the sequence of events triggered by UV irradiation of E. coli is as follows: UV radiation damages the DNA by creating lesions that mechanically disrupt the process of DNA duplication by stalling the DNA-polymerase (Pol III) in a moving replication fork. This, in turn, results in the production of single-stranded DNA (ssDNA) gaps. These gaps are coated by the protein RecA, forming long nucleoprotein filaments in which it assumes its active form, RecA*. RecA*, together with other proteins, is involved in the nonmutagenic filling in of ssDNA gaps via homologous recombination, and it catalyses the cleavage of the transcriptional repressor LexA and of the protein UmuD, whose cleaved form—UmuD′—is necessary for mutagenesis. The drop in the level of the transcription factor LexA, due to its cleavage, de-represses the regulon involved in the SOS response. This regulon comprises about 50 genes, including those encoding the mutagenesis proteins UmuD and UmuC, RecA, and LexA itself. Also part of the SOS regulon are genes encoding UvrA, B, C—a group of nucleotide excision repair (NER) proteins that locate and excise damaged regions from the DNA.
Mutagenesis in UV-irradiated E. coli cells is mainly the direct result of the activity of the error-prone DNA polymerase, Pol V. Pol V consists of two units of UmuD′ and one unit of UmuC. It inserts several random base pairs in the DNA strand directly opposite a lesion, thus helping a replication fork to quickly bypass the lesion, after which Pol III can take over and continue replication. A distinct coordinated subnetwork of proteins centered on UmuD and UmuC controls the abundance, and thereby the activity, of Pol V. 

In Escherichia coli, SOS boxes are 20-nucleotide long sequences near promoters with palindromic structure and a high degree of sequence conservation. The high information content of SOS boxes permits differential binding of LexA to different promoters and allows for timing of the SOS response. Logically, the lesion repair genes are induced at the beginning of SOS response. The error prone translesion polymerases, for example: UmuCD’2 (also called DNA polymerase V), are induced later on as a last resort. Once the DNA damage is repaired or bypassed using polymerases or through recombination, the amount of single-stranded DNA in cells is decreased, lowering the amounts of RecA filaments decreases cleavage activity of LexA homodimer which subsequently binds to the SOS boxes near promoters and restores normal gene expression.


ABBREVIATIONS:
SOS


OTHER NAME(S):
SOS response
SOS system
SOS repair
SOS box


DAMAGES RECOGNIZED AND REMOVED:


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ORTHOLOGY CLASS Homo sapiens L. (human) [HSA] Mus musculus L. (mouse) [MMU] Caenorhabditis elegans Maupas (nematode) [CEL] Drosophila melanogaster Meigen (fruit fly) [DME] Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE] Schizo-saccharomyces pombe Lindner (fission yeast) [SPO] Escherichia coli Migula (bacterium) K-12 MG1655 [ECO] Arabidopsis thaliana (L.) Heynh. (mouse-ear cress) [ATH]
ko:K02336 (DNA polymerase II [EC:2.7.7.7]) DNA Pol II
ko:K02336 (DNA polymerase II [EC:2.7.7.7]) DNA Pol II
ko:K03502 (DNA polymerase V) DNA Pol V
ko:K03503 (DNA polymerase V [EC:3.4.21.-]) UmuD
ko:K03703 (excinuclease ABC subunit C) UvrC
ko:K03702 (excinuclease ABC subunit B) UvrB
ko:K03701 (excinuclease ABC subunit A) UvrA
ko:K03111 (single-strand DNA-binding protein) SSBP1 Ssbp1 mtSSB Ssb At3g18580
ko:K02336 (DNA polymerase II [EC:2.7.7.7]) DNA Pol II
ko:K03631 (DNA repair protein RecN (Recombination protein N)) RecN
ko:K01356 (repressor LexA [EC:3.4.21.88]) LexA
ko:K03553 (recombination protein RecA) RecA recA3-like

References:

  • Error-prone DNA repair and translesion DNA synthesis. II: The inducible SOS hypothesis.
    Bridges BA.
    , 2005 , : [PUBMED]
  • Error-prone DNA polymerases: novel structures and the benefits of infidelity.
    Friedberg EC., Fischhaber PL., Kisker C.
    Cell, 2001 Oct, 107:9-12 [PUBMED]
  • Error-prone repair DNA polymerases in prokaryotes and eukaryotes.
    Goodman MF.
    Annu. Rev. Biochem., 2002 , 71:17-50 [PUBMED]
  • SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis.
    Radman M.
    , 1975 , : [PUBMED]
  • Structure of the UmuD' protein and its regulation in response to DNA damage.
    Peat TS., Frank EG., McDonald JP., Levine AS., Woodgate R., Hendrickson WA.
    Nature, 1996 Apr, 380:727-30 [PUBMED]
  • SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification.
    McKenzie GJ., Lee PL., Lombardo MJ., Hastings PJ., Rosenberg SM.
    Mol. Cell, 2001 Mar, 7:571-9 [PUBMED]
  • SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness.
    Yeiser B., Pepper ED., Goodman MF., Finkel SE.
    Proc. Natl. Acad. Sci. U.S.A., 2002 Jun, 99:8737-41 [PUBMED]
  • SOS response as an adaptive response to DNA damage in prokaryotes.

    , , : [PUBMED]
  • Reconstitution of an SOS response pathway: derepression of transcription in response to DNA breaks.

    , , : [PUBMED]
  • Lex marks the spot: the virulent side of SOS and a closer look at the LexA regulon.

    , , : [PUBMED]
  • The bacterial LexA transcriptional repressor.

    , , : [PUBMED]
  • Interconversion between bound and free conformations of LexA orchestrates the bacterial SOS response.

    , , : [PUBMED]

Last modification date: Oct. 21, 2011