Under Repair
The international Morse code distress signal is SOS – usually interpreted as Save Our Souls – but in bacteria, the SOS response is a DNA repair system involving the RecA and LexA proteins. The world is a nasty place for cells, full of hazardous chemicals and radiation such as ultraviolet light in sunlight which can easily damage DNA. Without mechanisms to repair such damage, the cell would be finished. The bacterial SOS system involves post-replication DNA repair and allows cells to bypass errors in their DNA.
As with many areas of cellular metabolism, the SOS response has been best studied in Escherichia coli. During normal growth, expression of approximately 40 SOS genes is negatively regulated by the LexA repressor protein. Under normal conditions, LexA binds to a 20-bp consensus sequence (called the SOS box) in the operator region of the SOS genes. Some SOS genes are expressed at low levels even in the repressed state, but if DNA is damaged, DNA polymerase activity is blocked at replication forks. In these circumstances, the RecA protein forms a filament around the single-stranded DNA generated at the damaged site. DNA-binding leads to activation of the dormant RecA protein, and the activated form of RecA acts as a protease which digests the LexA repressor. As the concentration of LexA decreases, repression of the SOS genes is gradually switched off, depending on the affinity of LexA for the SOS boxes in different genes. Operators that bind LexA weakly are the first to be fully expressed, whereas those which bind LexA strongly are only activated at very low LexA levels.
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A recent paper in Nature increased our knowledge of bacterial DNA repair mechanisms by describing how a bacteriophage enzyme (T7 endonuclease I) is able to help repair damaged DNA (The structural basis of Holliday junction resolution by T7 endonuclease I. Nature 2007 449: 621-624). During DNA repair or recombination, a structure known as a Holliday junction is formed. This structure is eventually repaired by a junction-resolving enzyme such as phage T7 endonuclease I.
DNA repair mechanisms are essential to all cells, which would not be able to survive for long without them. Consequently, they are also potential targets for antimicrobial compounds, and a better understanding of these processes might lead to new and useful antibiotics. DNA repair processes in bacterial cells are distinct from those in eukaryotic (e.g. human) cells, otherwise we would have no hope of being able to design drugs which would poison bacteria without poisoning us. At the same time, DNA repair is such an evolutionarily ancient process that there are many similarities between prokaryotic and eukaryotic cells. Understanding these process in bacteria brings us closer to understanding what goes on in human cells. It is estimated that every cell in your body suffers 10,000 DNA damaging events every day, probably more if you smoke or sunbathe, and some of those changes could lead to cancer or other diseases. A better understanding of DNA repair is of great importance in combating both infectious disease and in fighting cancer.
Tags: Antibiotics, Bacteria, Biology, Microbiology, Podcast, Science
