Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

Nagy, Gergely and Leveles, Ibolya and Vértessy G., Beáta (2014) Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool. FEBS JOURNAL, 281 (18). pp. 4207-4223. ISSN 1742-464X

Text febs12941_NTP_PPases_u_233747.846162.pdf Restricted to Registered users only Download (936kB) | Request a copy

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 alpha-phosphorus, it is shown that coordination of the gamma-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the beta-phosphorus atom mainly coordinate the alpha- and the beta-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.

Actions (login required)

Edit Item