Dna repair
Synonym(s)
DNA repair; DNA Repair; DNA repair mechanism; DNA repair mechanisms
DefinitionThis section has been translated automatically.
Enzymatically controlled processes that eliminate damage to DNA in various ways, thereby ensuring the smooth flow of DNA replication and transcription. DNA repairs are responsible for preventing mutations or polymorphisms from accumulating in the genome and thus becoming clinically relevant.
ClassificationThis section has been translated automatically.
Depending on the type of DNA repair or the damage repaired, 6 different repair mechanisms are known:
- Direct repair
- Base excision repair
- Nucleotide Excision Repair (NER)
- mismatch repair
- String break repair
- "Damage By-pass"
General informationThis section has been translated automatically.
- In the human body DNA is damaged by radiation, viruses, bacteria, mobile genetic elements ("jumping genes") and also by the duplication of DNA. These spontaneous changes or recombinations of the DNA ( mutations) are mostly of short duration. The damage is usually repaired in a short time by the cell's own DNA repair mechanisms, because the stability of the DNA is absolutely essential for life. The importance of DNA repair can be seen from the fact that DNA is the only molecule in humans that is specifically repaired.
- Proofreading: Inappropriate bases of a newly synthesized DNA strand can be cut out by a special polymerase (proofreading enzyme). This enzyme recognizes the new DNA strand by the degree of methylation of adenine. The defective sequence is then replaced by polymerase I and inserted by the DNA ligase
- Excision repair of modified bases: Especially UV light causes changes in the nucleotides (often formation of thymine dimers in the same DNA strand), these are excised by endonucleases, replaced by repair synthesis using polymerases with the correct sequence and reconnected to the DNA strand by ligases.
- Direct repair of modified bases by photoreactivation: Similar to 2, the binding of the dimers is weaker here so that they can be separated by photoreactivation. In the dark, the enzyme photolyase binds to the dimers, which are split into monomers under the influence of light.
- Repair by recombination during replication: Damaged areas in the DNA strand must be repaired quickly before a new replication round. If this is not possible, the repair can also be carried out by crossing-over. The necessary pending repair can then be carried out using information from the intact strand.
- SOS-Repair:If very many mutations occur simultaneously, this very faulty repair system, which requires the presence of UV-rays, is induced. For example, defective dimers are also replicated here, which cannot be detected later.
PrognoseThis section has been translated automatically.
- The DNA repair mechanisms developed phylogenetically at an early stage and have been optimized during evolution. It can be assumed that they are similar in all organisms. For example, a defect in DNA repair in humans causes the autosomal recessive genetic disease Xeroderma pigmentosum. Here, excisional repair (NER) is disturbed, so that multiple carcinomas of the skin develop after UV exposure (see photocarcinogenesis below).
- Damage to the DNA can be caused spontaneously in the course of DNA replication or by exposure to mutagenic substances, intense heat or ionizing radiation. For example, treatment with 1 Gy of X-rays per cell produces about 1000-2000 base modifications, 500-1000 single-strand breaks, 800-1600 changes in the sugar skeleton, 150 DNA-protein cross-links, 50 double-strand breaks.
- Furthermore, UV radiation can cause mutations. Single-stranded DNA shows an absorption maximum at 280 nm (UVB). UV-B as well as UV-A can indirectly damage the DNA by the formation of reactive oxygen radicals. Reactive oxygen radicals cause oxidative DNA damage to the DNA, which in turn leads to mutations. DNA errors can lead to the defective replication of the DNA for mitosis. Depending on the error code, certain proteins can therefore no longer be synthesized at all or only incorrectly.
- If the various repair mechanisms do not lead to success, they accumulate in growing DNA and protein errors (see also Muir-Torre syndrome; see also microsatellite instability). This results in various disorders of physiological cell function. Various "control proteins" of the cells recognize these DNA errors and induce a cycle stop or cell death ( apoptosis).
Note(s)This section has been translated automatically.
Examples of DNA damage repair
- Base excision repair: This is used to repair an error in the base pairing of one of the two DNA strands. The base in question is removed by a DNA glycosylase, then it is excised by an AP endonuclease and a phosphodiesterase. A DNA polymerase synthesizes the correct base depending on the complementary base on the faultless strand. A DNA ligase incorporates the new base into the DNA strand, thus correcting the error.
- Nucleotide excision repair: There are two different forms of nucleotide excision repair (NER). The first is Global Genome Repair (GGR), which repairs damage in transcriptionally inactive regions of the DNA; the second is Transcription Coupled Repair (TCR), a repair mechanism that repairs damage to the DNA currently being transcribed. These two forms differ only in the recognition of damage.
- Proofreading by DNA polymerase (base mismatch repair): The protein responsible for copying DNA, DNA polymerase, has the ability to check the new DNA strand during synthesis and compare it with the original strand. If it detects defective nucleotides, these are cut out and re-synthesized. A defect in mismatch repair causes hereditary non-polyposis colon carcinoma.
LiteratureThis section has been translated automatically.
- Berking C (2007) Photocarcinogenesis. dermatologist 58: 398-405
- Emmert B et al (2011) Xeroderma pigmentosum. dermatologist 62: 91-97