DNA Repair

DNA repair mechanisms had a very important role in ensuring the stability of genome. They are able to correct about 99% of transcription errors. The frequency of mismatches (incorrect pairing of basis) is about 1:107 nucleotides.

During the day thousands and thousands changes is occuring. For its reparation, at least one of the DNA chains has to be intact. The damaged part then can be synthesize again.

When the mismatch is appeared, it is neccesary to cut out the affected region of DNA and to synthesize the new one. If DNA repair mechanisms don´t do this, the mutation is transmitted to the next generation.

DNA Repair

 * Damage DNA is recognized by specific enzymes - nucleases. The covalent bond is interrupted and the gap occurs.
 * DNA-polymerase binds to the 3´end of DNA and fill the gap according to complementary strand.
 * DNA-ligase reunites the repaired part to the original strand.

Direct Reversal
For this repair mechanism it is not neccesary to break the DNA backbone. The most mistakes are caused by methyl group (-CH3). It changes C (cytosin) to T (thymin). This problem is solved by enzymes - glycosylases - which are able to restorate it.

Excision Repair
DNA strand has to be discontinued in order to be repaired.
 * Base Excision Repair (BER)
 * Nucleotide Excision Repair (NER)
 * Mismatch Repair (MMR)

Types of DNA Damage

 * 1) Modification of bases (lost of amino group)
 * 2) Mismatches of the normal bases (failure of DNA replication)
 * 3) Breaks of backbone of DNA (the most common cause is radiation)
 * 4) Cross-links (linkage between bases)

The damage of DNA should have more reasons:
 * chemical changes of DNA structure (nitrogen)
 * physical damages (UV light, radiation)
 * viral damages

Diseases with Defects in DNA Repair
In past it was discovered that there is a connection between DNA repair defects and developing of cancer (especially gut cancer). The heredity of repair genes is recessive. That means that each person has two different copies of the gene (one from each parent) and it´s neccesary to damage both of them to disease outbreak.


 * Hereditary Nonpolyposis Cancer Syndome (HNCS)
 * Disease which is connected with defect of DNA mismatch repair. Normally the incorrect pairing is repaired. But in this case the errors are accumulated in the cells. Tumor supresive and protooncogenes are affected too. This leads to increased risks of developing cancer. Patients with defect of mismatch repair have typically microsatellite instability.


 * Xeroderma Pigmentosum (XP)
 * Patients with XP have an increased risks of skin cancer. The reason is inability to repair the cross-linking of pyrimidine pairs, which arise from UV-light influence.


 * Fanconi anemia, Bloom Syndrome, Ataxia-Teleangiectasia
 * Autosomal recessive diseases which are connected with damage of recombination repair genes. DNA is more sensitive to external agents.

Related articles

 * Xeroderma Pigmentosum
 * Hereditary Nonpolyposis Cancer Syndrome
 * Base