Abstract
Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by a set of master transcription factors but also at the enzyme level by allosteric regulation and feedback inhibition. Here we review the cellular demands of nucleotide biosynthesis, their metabolic pathways and mechanisms of regulation during the cell cycle. The use of stable isotope tracers for delineating the biosynthetic routes of the multiple intersecting pathways and how these are quantitatively controlled under different conditions is also highlighted. Moreover, the importance of nucleotide synthesis for cell viability is discussed and how this may lead to potential new approaches to drug development in diseases such as cancer.
Document Type
Article
Publication Date
2-27-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.1093/nar/gkv047
Repository Citation
Lane, Andrew N. and Fan, Teresa W-M, "Regulation of Mammalian Nucleotide Metabolism and Biosynthesis" (2015). Toxicology and Cancer Biology Faculty Publications. 34.
https://uknowledge.uky.edu/toxicology_facpub/34
Supplementary Tables and Figures
Notes/Citation Information
Published in Nucleic Acids Research, v. 43, issue 4, p. 2466-2485.
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.