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JOURNAL OF BACTERIOLOGY, Dec. 2007, p. 8793 8800 0021-9193/07/$08.00 0 DOI:10.1128/JB.01361-07 Copyright 2007, American Society for Microbiology. All Rights Reserved. Vol. 189, No. 24 The Micrococcus

While there has been a general recognition of the role of DNA replication inhibition in disease prevention, most of the data supporting it come from animal studies, where the ability of the inhibitor is already established, and from studies of cancer patients where DNA replication is inhibited at the time of diagnosis. Studies of genetic mechanisms of developmental delays and disease have so far focused on DNA replication initiation and maintenance, with little consideration given to the role of DNA replication. This article is an important first step towards clarifying the mechanisms of DNA replication in Malthusian development and the importance of DNA replication inhibition in disease prevention. Studies using two different agents, an inhibitor of DNA replication and DNA replication induction, led us to conclude that DNA replication inhibition by the inhibitor is responsible for the inhibition of the growth of cells in the culture medium, in contrast to data obtained from the use of inhibitors of DNA replication (i.e., DNA replication activator). This result suggests that DNA replication inhibition can influence the development of a cell in such a manner as to eliminate or weaken other developmental processes. This important observation leads us to propose the following hypothesis concerning the molecular mechanism of inhibition of DNA replication: DNA replication inhibition by the activator is responsible for inhibition (or “delay”) in the growth of the cells in the culture medium. The inhibitory effect of the activator is not mediated by direct inhibition of replication but by its ability to suppress other developmental processes such as cell cycle progression and/or cell differentiation. If this is correct, the inhibitory effect of the activator would be most pronounced during the early stages of maturation, leading to delayed development, while the inhibition of DNA replication would be most evident early in development, leading to delayed replication.

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