DNA Repair Proteins

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DNA Repair Proteins

DNA Repair Proteins Background

DNA repair is a reaction of cells to DNA damage. This reaction may restore the structure of DNA and perform its original function again; but sometimes it does not completely eliminate DNA damage, it just makes cells tolerate this DNA. Damage can continue to survive. Maybe the damage that has not been fully repaired will be displayed under suitable conditions (such as the canceration of cells), but if the cell does not have this repair function, it cannot cope with the DNA damage events and cannot survive. Therefore, studying DNA repair is also an important aspect of exploring life, and it is closely related to military medicine and oncology.

  1. Mismatch repair (MMR)

    Mismatch repair can correct occasional DNA base mismatches in non-homologous chromosomes during DNA replication and recombination. Mismatched bases can be identified and repaired by mismatch repair enzymes.

    Diagram of DNA mismatch repair pathways. Figure 1. Diagram of DNA mismatch repair pathways.
  2. Light repair

    This is the earliest discovered DNA repair method, which means that the cell directly repairs the damaged DNA under the action of an enzyme. Repair is performed by DNA photolyase in bacteria. This enzyme can specifically recognize and bind dimers that are covalently bound to adjacent pyrimidines on the nucleic acid chain caused by ultraviolet light. Light; if it is irradiated with light with a wavelength of 300-600nm after binding, the enzyme is activated, the dimer is broken down into two normal pyrimidine monomers, and then the enzyme is released from the DNA strand, and the DNA restores its normal structure. Later, similar repair enzymes were found to be widespread in plants and animals, as well as in human cells. DNA photolytic enzymes can be activated by visible light (300-600 nm, 400 nm is the most effective), and decompose the pyrimidine dimer formed by ultraviolet radiation. This enzyme is widely present, but the human body only exists in lymphocytes and skin fibroblasts, and is a secondary repair method.

  3. Excision repair

    (1) There are many kinds of specific endonucleases in the cell, which can identify the damaged part of DNA, cut the single strand of DNA in the vicinity, and then cut the damaged strand by exonuclease, and the polymerase uses the complete strand as a template perform repair synthesis and finally seal with ligase.

    (2) Uracil, xanthine and hypoxanthine formed by base deamination can be excised by a specific N-glycosidase, and then use AP (apurinic / apyrimidinic, apurin or apyrimidin) endonuclease to turn on the phosphate Diester bond for excision repair. Consumption of NADPH to synthesize thymine during DNA synthesis can be distinguished from uracil formed by cytosine deamination, which improves the fidelity of replication. RNA is not repaired, so “cheap” uracil is used.

    (3) Excision repair does not require light, also called dark repair. There is the UvrABC system in E. coli, which can remove and repair pyrimidine dimers. The lack of a corresponding system in the human body causes "pigmented dry skin disease". The skin is dry, pigmented, and susceptible to skin cancer. T4 endonuclease can be added for treatment.

    Nucleotide excision repair Figure 2. Nucleotide excision repair
  4. Rejoining

    DNA single-strand breaks are common damages, and some of them can be completely repaired only by the participation of DNA ligase. This enzyme is ubiquitous in all kinds of organisms and various cells, and the repair reaction is easy to proceed. But double-strand breaks can hardly be repaired.

    Structure of the base-excision repair enzyme uracil-DNA glycosylase excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow. Figure 3. Structure of the base-excision repair enzyme uracil-DNA glycosylase excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow.

DNA Repair Proteins

Ada, also known as adaptive protein, can recognize methylated DNA and transfer methyl groups to its own cysteine. It is irreversible, so it is called "suicide repair". Repairs methyl groups on phosphate and guanosine. This phenomenon is called adaptive response, hence the name. Ada transfers alkyl groups from DNA bases and sugar phosphate backbones to cysteine residues, thereby inactivating itself. Therefore, it is called a suicide enzyme because it reacts stoichiometrically with its substrate instead of catalyzing it. The methylation of Ada protein converts it into an auto-transcriptional activator, inducing the expression of its own genes and other genes, which together with Ada can help cells repair alkylation damage.

Reference:

  1. Fuss JO.; et al. DNA repair: dynamic defenders against cancer and aging. PLoS Biology. 2006, 4 (6): e203.

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