DNA ligase is an enzyme essential for DNA replication, repair and recombination in all organisms [1][2][3]. The enzyme catalyzes the formation of phosphodiester bonds at single-strand breaks in duplex DNA during these physiological processes [1][2][3]. There are two classes of DNA ligases, identified on the basis of their cofactor requirements. Bacterial DNA ligases involved in DNA replication utilize NAD + as a cofactor, whereas mammalian and viral DNA ligases require ATP for activity [1][2][3]. Biochemical studies of bacterial DNA ligase (NAD + -dependent), and viral and human DNA ligases (ATP-dependent) have established that the mechanism of the reactions catalyzed by the two different groups of DNA ligases is similar [1][2][3]. The reaction mechanism consists of three reversible steps: (a) adenylation of the enzyme by transferring the adenylate group from NAD + or ATP to the e-NH 2 group of Lys in the enzyme with the release of nicotinamide + and specifically inhibits enzyme adenylation, but not DNA adenylation or ligation. Labeling studies establish that this molecule inhibits the incorporation of thymidine into DNA and that overexpression of DNA ligase in the cell abolishes this inhibition. Finally, microbiological studies show that this molecule exhibits a broad spectrum of antibacterial activity. Together, this study shows that this small molecule inhibitor identified is specific to bacterial NAD + -dependent DNA ligases, exhibits a broad spectrum of antibacterial activities, and has the potential to be developed into an antibacterial agent.Abbreviations DDPP, 2,4-diamino-7-dimethylamino-pyrimido [4,5-d]pyrimidine; FRET, fluorescence resonance energy transfer; NMN, nicotinamide mononucleotide.

From a multi-study Bain & Company search to identify the most reliable principles on which to base a strategy for pro®table growth, two key insights emerged. The ®rst is that the most promising growth opportunities tend to lie adjacent to the core business. Indeed, the farther away from the core business companies extend themselves in pursuit of growth, the worse they tend to fare. The second insight, and the one focused on here, is that the competitive strength of the core business itself is a crucial factor in the success of growth initiatives. The principle message of this article is that companies should ®rst re-examine the strength of their core business before they attempt to expand beyond it. Even if the core business is a market leader, it may need to seek even greater competitive advantage before essaying major growth initiatives. If it's well behind the market leaders, its position can be greatly strengthened through consolidation, upwards or downwards. The result will be a sounder, more reliable base for growth. The cases featured here help show the way.A chief concern of senior executives these days is ®nding new sources of sustained and pro®table growth. Yet choosing between investing in a proven business versus a potential one requires careful analysis and study of both successful and failed attempts. Recent Bain & Company research shows that overreaching for growth in areas adjacent to a ®rm's core business is often destructive.To put the successful and failed attempts into historical perspective, consider the starkly contrasting investment choices on expansion into markets adjacent to their core businesses taken by Kmart and Wal-Mart in the 42 years after both chain stores opened their ®rst stores in 1962. Wal-Mart made a series of methodical moves into such adjacencies as Sam's Club, electronics, and overseas stores, one by one. Kmart overreached with adjacency moves ranging from books (Walden) to sporting goods (Sports Authority) and a chain of department stores in Czechoslovakia. Though there are many causes of the two ®rm's different fortunes,`A ccording to Bain's recent ®ve-year study of 1,850 companies, the chances for success in growth initiatives were nearly three times higher for companies moving into adjacencies from strong leadership positions in their core business. ''

Too many companies are slow to respond when growth hits a wall. Chris Zook and James Allen believe you can renew your core business by tapping into hidden assets.

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