A Never-Ending Story

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Science  17 Sep 2010:
Vol. 329, Issue 5998, pp. 1475-1476
DOI: 10.1126/science.1196347

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More than 50 years ago, Reichard and colleagues elucidated how cells make their DNA building blocks—the deoxyribonucleotides or dNTPs (1). They found that the enzyme ribonucleotide reductase (RNR) converts ribonucleotides (RNA building blocks) to corresponding dNTPs. One would expect that such a central pathway for all living cells would be meticulously mapped by now. Yes—and no. Researchers have described several classes and subclasses of RNRs (see the figure) that appear to have the same evolutionary origin (25), but involve different chemical cofactors, and so enable cells to construct dNTPs under different environmental conditions. Whenever the field seems settled, however, fascinating new aspects appear (1, 2). On page 1526 of this issue, Boal et al. (3) report crystal structures of RNR complexes from the bacterium Escherichia coli that, together with earlier studies, confirm and neatly illuminate yet another way cells can construct dNTPs, this time with the help of manganese (Mn).