Role of magnesium in genomic stability

In cellular systems, magnesium is the second most abundant element and is i nvolved in basically ah metabolic pathways. At physiologically relevant con centrations, magnesium itself is not genotoxic, but is highly required to m aintain genomic stability. Besides its stabilizing effect on DNA and chroma tin structure, magnesium is an essential cofactor in almost all enzymatic s ystems involved in DNA processing. Most obvious in studies on DNA replicati on, its function is not only charge-related, but very specific with respect to the high fidelity of DNA synthesis. Furthermore, as essential cofactor in nucleotide exercision repair, base excision repair and mismatch repair m agnesium is required for the removal of DNA damage generated by environment al mutagens, endogenous processes, and DNA replication. Intracellular magne sium concentrations are highly regulated and magnesium acts as an intracell ular regulator of cell cycle control and apoptosis. As evident from animal experiments and epidemiological studies, magnesium deficiency may decrease membrane integrity and membrane function and increase the susceptibility to oxidative stress, cardiovascular heart diseases as well as accelerated agi ng. The relationship to tumor formation is more complex; magnesium appears to be protective at early stages but promotes the growth of existing tumors . With respect to the magnesium status in humans, the daily intake in most industrialized countries does not reach the current recommended daily dieta ry allowances (RDA) values, and thus marginal magnesium deficiencies are ve ry common. (C) 2001 Elsevier Science B.V. All rights reserved.