Enzymatic repair systems

An in-depth study of DNA repair systems (Aravind et al., 1999a) has concluded that few, if any, repair proteins occur with identical collinear domain arrangements in all three kingdoms of life. Approximately 10 enzyme families of adenosine triphosphatases (ATPases), photolyases, helicases, and nucleases were identified that are all likely to have been present in the cenancestor. These enzymatic domains are accompanied in DNA repair proteins by numerous regulatory domains. This indicates that the domain architectures of these proteins are labile, with incremental addition and/or subtraction of domains to conserved cores to be a common phenomenon except in the most closely related species. 

The chemistry of DNA damage is diverse and complex. The cellular response to this damage includes a wide range of enzymatic systems that catalyze some of the most interesting chemical transformations in DNA metabolism. We first examine the effects of alterations in DNA sequence and then consider specific repair systems. 

Cells have two defense systems to cope with free-radical DNA damage that work on very different time scales the fast chemical repair by thiols that occurs at the stage of DNA free-radicals and the slow enzymatic repair that only sets in once the damage is fully set. The present book deals in some detail with the chemical repair. To discuss the even more important enzymatic repair would have exceeded the space allocated to this book, and enzymatic repair is only briefly touched on. 

We now know that in bacteria, yeast, and mammalian cells, there are enzymatic systems that can repair damaged DNA. These systems are known as DNA repair systems. 

Moser MJ, Prudent JR (2003). Enzymatic repair of an expanded genetic information system. Nucleic Acids Res., 31 5048-5053. 

ET is also involved in a range of other processes of synthetic interest, a number of which centre on ring-opening reactions of small strained ring systems. In addition to its synthetic potential the oxidative cycloreversion of oxetanes is of biological importance as it is involved in the enzymatic repair of... 

The fact that the antioxidant and the enzymatic protective system complement one another in radical detoxification possibly indicates some repair properties of the antioxidants towards oxidized amino acids [6 or results from the recycling of oxidized a-tocopherol by the glutathione-ascorbate-system (7J. 

The A radical can disproportionate to ascorbate and dehydroascorbic acid or be enzymatically reduced back to AH" by an NADH-dependent system (57), therefore the following repair mechanism was proposed (56) for potentially damaging organic free radicals ... 

It is well known that protein-Cr -DNA, amino acid-Cr -DNA, and DNA-Cr -DNA cross-links form in cells and organisms exposed to Cr(VI) (Section III.B.4). The potential importance of Cr -DNA lesions in Cr(VI) induced genotoxicity is determined by the following (1) kinetically inert (80) Cr(III) complexes with DNA and other bioligands are less likely to be recognized and repaired by enzymatic systems than oxidative DNA damage and (2) Cr(III) complexes can accumulate in cells of Cr(VI) exposed individuals over many years (431). Interactions of Cr(III) complexes with isolated DNA and nucleotides have been studied in order to elucidate the structures and biological roles of such crosshnks (250, 356). 

Species, sex, age, genetics, e.g., variability in enzymatic factors such as polymorphisms (cytochrome systems) or tissue repair mechanisms ... 

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