Overview

Every cell's genome is vulnerable to change. DNA-modifying chemicals and electromagnetic radiation continually damage it, and the inherent inaccuracy of DNA synthesis erodes its perfect replication. There are two main lines of defense against DNA damage: prevention and repair. Preventive mechanisms (e.g., natural sunscreens, enzymatic degradation of mutagens) go beyond the scope of this book. The enzymes of DNA repair and their modes of action are described here.

Systems of Repair

Every organism has multiple systems to repair premutational alterations to DNA – both damage and mispaired nucleotides. For example, Drosophila has nearly 90 DNA repair enzymes. Systems of repair, some of which are universal among organisms and some of which are not, fall into broad categories:

• Direct repair – the sugar-phosphate backbone remains intact (this is the only nonsurgical option for repairing DNA damage)

• Repair of apurinic and apyrimidinic sites (AP repair) – excision of a short sequence of one strand containing an AP site (nucleotide missing its base)

• Mismatch repair – a region containing a mismatched base is removed and replaced, usually repairing a newly synthesized strand.

• Excision repair – uses exinucleases, which are endonucleases that nick a single strand of DNA on both sides of an altered site

• Recombination repair – uses recombination to fill gaps in DNA

• End-joining repair – joins double-strand breaks in DNA

Direct Repair

The two kinds of repair of altered nucleotides, which does not involve breaking the sugar-phosphate backbone of DNA, are photoreactivation of pyrimidine dimers and dealkylation of alkylated bases.