Chapter 30 : Nucleotide Metabolism and DNA Replication

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The first edition of ( ) was published very shortly after the release of the complete genome sequence of H37Rv ( ). Armed with that resource, we searched for genes that might be involved in mycobacterial nucleotide metabolism and DNA replication ( ). Our analysis at the time relied entirely on the homology-based identification of genes that had been discovered and characterized in other organisms; however, by confirming the presence, or suggesting the absence, in of homologs of genes of known function, it provided a useful framework for subsequent studies of the reactions and pathways underlying nucleotide metabolism and DNA replication in this major human pathogen. At that stage, the field of mycobacterial genetics was in its infancy, and little was known about the function of individual mycobacterial genes and their encoded proteins in these or other metabolic pathways. However, over the past 13 years, spectacular technical advances have been made that have had a massive impact on the broader field of general bacteriology and, more importantly in the context of this book, have driven the postgenomic revolution in our understanding of fundamental mycobacterial physiology and metabolism. The development, in particular, of a powerful toolkit for random, targeted, and conditional mutagenesis of mycobacterial genomes has allowed gene function to be probed under a variety of conditions. In turn, this has enabled the compilation of catalogs of genes (conditionally) essential for mycobacterial growth and/or survival, while providing new insights into the biology of mycobacteria.

Citation: Warner D, Evans J, Mizrahi V. 2014. Nucleotide Metabolism and DNA Replication, p 635-656. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0001-2013
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Figure 1

Pathways for the formation of dTTP in . The steps for which homologs are absent are shown in gray, and enzymes that are essential for growth are shown in shaded boxes. Adapted from references and .

Citation: Warner D, Evans J, Mizrahi V. 2014. Nucleotide Metabolism and DNA Replication, p 635-656. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0001-2013
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Generic image for table
Table 1

Genes involved in purine and pyrimidine salvage pathways in

Citation: Warner D, Evans J, Mizrahi V. 2014. Nucleotide Metabolism and DNA Replication, p 635-656. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0001-2013
Generic image for table
Table 2

Genes known to be involved in DNA replication in

Citation: Warner D, Evans J, Mizrahi V. 2014. Nucleotide Metabolism and DNA Replication, p 635-656. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0001-2013

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