DNA Repair

The integrity of DNA is under constant assault from radiation, chemical mutagens, and spontaneously arising changes. In spite of this onslaught of damaging agents, the rate of mutation remains remarkably low, thanks to the efficiency with which DNA is repaired. It has been estimated that fewer than one in a thousand DNA lesions becomes a mutation; all the others are corrected.

There are a number of complex pathways for repairing DNA, but several general statements can be made about DNA repair. First, most DNA repair mechanisms require two nucleotide strands of DNA because most replace whole nucleotides, and a template strand is needed to specify the base sequence. The complementary, double-stranded nature of DNA not only provides stability and efficiency of replication, but also enables either strand to provide the information necessary for correcting the other.

A second general feature of DNA repair is redundancy, meaning that many types of DNA damage can be corrected by more than one pathway of repair. This redundancy testifies to the extreme importance of DNA repair to the survival of the cell: it ensures that almost all mistakes are corrected. If a mistake escapes one repair system, it's likely to be repaired by another system.

We will consider four general mechanisms of DNA repair: mismatch repair, direct repair, base-excision repair, and nucleotide-excision repair (Table 17.5).

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