Figure 5.5. DNA repair.
position. DNA ligase then seals the strand by catalyzing the reformation of a phosphodiester link.
A bacteriophage called PBS2, which infects the bacterium Bacillus subtilis, is unusual in that it uses uracil in place of thymine in its DNA. This would be expected to have the unfortunate result—for the virus—that as soon as the bacteriophage DNA entered the bacterial cytoplasm, bacterial repair enzymes would begin cutting the uracils out. PBS2 gets around this problem by quickly making a protein called uracil glycosylase inhibitor, which binds irreversibly to the bacterium's uracil DNA glycosylase and inactivates it. Once this DNA repair enzyme is inactivated, the next problem is to persuade the bacterium to make lots of uracil nucleotides rather than thymine ones. Thymine is normally made from uracil, so all PBS2 does is to produce a second protein that inhibits this conversion, ensuring a good supply of dUTP for replication of its DNA.
Nucleotide excision-repair is required to correct a thymine dimer. The thymine dimer, together with some 30 surrounding nucleotides, is excised from the DNA. Repairing damage of this bulky type requires several proteins because the exposed, undamaged, DNA strand must be protected from nuclease attack while the damaged strand is repaired by the actions of DNA polymerase I and DNA ligase.
Medical Relevance 5.2
Bloom's Syndrome and Xeroderma Pigmentosum
DNA helicases are essential proteins required to open up the DNA helix during replication. In Bloom's syndrome, mutations give rise to a defective helicase. The result is excessive chromosome breakage, and affected people are predisposed to many different types of cancers when they are young.
People who suffer from the genetic disorder known as xeroderma pigmentosum are deficient in one of the enzymes for excision repair. As a result, they are very sensitive to ultraviolet light. They contract skin cancer even when they have been exposed to sunlight for very short periods because thymine dimers produced by ultraviolet light are not excised from their genomes.
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