DNA Repair : Base excision repair

DNA bases can be altered, either spontaneously, as is the case with cytosine, which slowly undergoes deamination (the loss of its amino group) to form uracil, or by the action of deaminating or alkylating compounds. For example, nitrous acid, which is formed by the cell from precursors such as the nitrates, deaminates cytosine, adenine (to hypoxanthine), and guanine (to xanthine). Dimethyl sulfate can alkylate (methylate) adenine. Bases can also be lost spontaneously. For example, ~10,000 purine bases are lost this way per cell per day. Lesions involving base alterations or loss can be corrected by base excision repair ([BER], Fig. 1).

Figure 1:  Correction of base alterations by base excision repair. C = cytosine; U = uracil; NH3 = ammonia; PPi = pyrophosphate.
1. Abnormal base removal: In BER, abnormal bases, such as uracil, which can occur in DNA by either deamination of cytosine or improper use of dUTP instead of dTTP during DNA synthesis, are recognized by specific DNA glycosylases that hydrolytically cleave them from the deoxyribosephosphate backbone of the strand. This leaves an apyrimidinic site, or apurinic if a purine was removed, both referred to as AP sites.
2. AP site recognition and repair: Specific AP endonucleases recognize that a base is missing and initiate the process of excision and gap filling by making an endonucleolytic cut just to the 5′-side of the AP site. A deoxyribose phosphate lyase removes the single, base-free, sugar phosphate residue. DNA pol I and DNA ligase complete the repair process.

مواضيع ذات صلة

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