Enzymes That Incise Damaged DNA

This chapter focuses on DNA-incising activities from Escherichia coli. E.coli has been the subject of extensive genetic and biochemical investigations on the excision repair of DNA. The excision of damaged or inappropriate nucleotides from DNA can occur by a number of different biochemical pathways, depending on both the nature of the specific base damage in question and on the particular organism under investigation. Most pathways of excision repair of DNA include the enzyme-catalyzed hydrolysis of phosphodiester bonds by specific enzymes. Such enzymes can be divided into two major classes (1) those that attack phosphodiester bonds in DNA subsequent to the hydrolysis of the associated glycosylic bond that links a nitrogenous base to the deoxyribose-phosphate backbone and (2) those that directly attack phosphodiester bonds in damaged DNA. The former class of enzymes is designated as apurinic/apyrimidinic (AP) endonucleases because their endonuclease activity is confined to sites of base loss in DNA. Such substrate sites arise by the spontaneous hydrolysis of N-glycosylic bonds in DNA, or by enzyme-catalyzed hydrolysis of these bonds by DNA glycosylases.