Articles :: Diseases and Gene :: Repairing DNA damage

Repairing DNA damage

Photoreactivation

An enzyme called photoreactivating enzyme (or DNA photolyase) detects pyrimidine dimers. It then combines to the site of damage and breaks the dimer.

Photoreactivation enzyme absorbs light of wavelength greater then 300 nm to get energy to break the dimer. Since light is needed, this kind of repair is called photoreactivation repair.

Repairing damage caused by alkylating agents

An example of this kind of repair is the enzyme O6 methylguanine methyl transferase. When it detects a base is alkylated by an alkylating agent, it combines with the alkyl group and removes it. The base is thus restored.

(You may question that the enzyme is changed and that does not meet the definition of an enzyme that enzyme are not used up in any reactions. Enzymes like O6 methylguanine methyl transferase are called suicide enzymes. As one repair costs a protein molecule, this kind of repair is quite high-priced.)

Mismatch repair

Using deamination of cytosine as an example, cytosine is converted to uracil. But uracil is normally present in RNA only, not DNA. The error is quite simple to detect (though the mechanism of detection is still unknown). Upon detection, DNA glycosylase cuts the glycosidic bond between uracil and the sugar. Uracil is removed to left an AP site.

Then AP endonucleases cut off the sugar and the phosphate. DNA polymerase will insert the correct nucleotide to the broken part according to the opposite helix and the nick left after will be fused by DNA ligase.

This method can also be applied to repair AP sites.

Excision repair

While mismatch repair involves cutting of one single nucleotide, excision repair cuts off 12-13 nucleotides called olignucleotide. Excision repair is directed by a collection of enzyme called the excinuclease.

One kind of excision repair is directed by the uvrABC (ultraviolet repair) endonucleases, which are the products of uvrA, uvrB and uvrC genes respectively to fight against dimers.

When the dimer is detected, an olignucleotide which the dimer is in is cut off. DNA polymerase I will fill up the gap left behind and eventually DNA ligase will seal the nicks.


  excision repair  
  Drawn by ourselves  



Recombinational repair

Sometimes a defected gene can be tolerated rather then being repaired immediately. Recombinational repair is an example.

It is also called postreplication repair because it operates when the DNA is replicated.

When there is a dimer in the DNA, during replication, the dimer stops the action of DNA polymerase. Nevertheless, the replication will continue though but a gap will be made on the replicated DNA. The recA protein directs the defected replicated gene to exchange material with the genetic material with its healthy twin.

Its healthy twin will have a gap since some of the genetic material is transmitted to the defected one. But the gap can be easily filled in by DNA polymerase with reference to the other duplex.

Recombination repair allows the DNA to replicate in spite of the dimer. The dimer can be repaired sooner or later.

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