title: Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool.
abstract: The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the α-phosphorus, it is shown that coordination of the γ-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the β-phosphorus atom mainly coordinate the α- and the β-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary; Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Hungary.
authors: Gergely N
authors: GN
authors: Nagy
authors: Ibolya
authors: I
authors: Leveles
authors: Beáta G
authors: BG
authors: Vértessy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D016384:Consensus Sequence; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000502:physiology; D003854:Deoxyribonucleotides / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000502:physiology*
chemical_list: D003854:Deoxyribonucleotides; D010744:Phosphoric Monoester Hydrolases; D045643:DNA Repair Enzymes
keywords: DNA repair; NTPases; X-ray crystallography; non-canonical nucleotides; nucleophilic attack