Nucleic Acids in the Storage and Transmission of Genetic Information

The role of DNA and RNA in the storage and transmission of genetic information is well established and can be found in standard textbooks. The hereditary material in the nucleus of human cells is packed into 23 chromosomes, and additional DNA is found in the mitochondria. The human genome is known to contain approximately 30 000 coding sequences, or genes, and a substantial proportion of DNA has a regulatory role in transcription of the genes. The sequence of the four bases and the capacity of DNA to be copied into two complementary strands underlie the genetic information of all living organisms. Interactions between DNA and the transcription factors determine the time and place in the body where genes are transcribed, causing development and metabolism to occur.

RNA molecules are synthesized initially on a DNA template by a DNA-dependent RNA polymer-ase in a process called transcription, in which ribo-nucleotides complementary to the bases of one strand of DNA are joined by 3'-5' phosphodiester bonds.

Cells contain three types of RNA, each of which is chemically modified after transcription from the DNA template. The three kinds of RNA together are important in the translation of the genetic message to synthesize proteins in the cell. Most RNA is in the cytoplasm, principally in the form of riboso-mal RNA (80% of the total), which performs structural and catalytic roles in ribosomes, the site of the growing polypeptide chain in protein synthesis, whereas messenger RNA (5%) provides the template for protein synthesis. The amino acids are brought to the assembly site covalently bonded to transfer RNA (15%), with their order in the growing protein being specified by the order of the bases in mRNA.

Synthesis of nucleic acids and their precursors in different human cells is related to cellular function

Synthesis of both DNA and RNA is prominent in cells and tissues with a high rate of turnover or metabolism (e.g., liver, gut epithelium, skin, dividing lymphocytes, bone marrow, and hair follicles). In most tissues in the adult, cells differentiate to perform specialized tasks and therefore cell division is used only to replace cells that have been lost. Different complements of enzymes are expressed in each cell type, and therefore tissues have characteristic profiles of internal metabolites, including nucleotides and nucleosides.

For example, in cells that do not continuously divide, such as heart and muscle, nucleotide profiles are relatively simple, relating to the major requirement to sustain levels of cofactors and ATP. In contrast, rapidly dividing cells in liver and intestine show a complex nucleotide pattern, supporting these organs as major sites of nucleic acid metabolism. The gut is particularly important in this respect. The rate of cell turnover in the luminal villi is high, and it has been calculated in rat that approximately 30 mg of endogenous nucleic acid from dead cells enters the gut lumen daily. This means that the rate of nucleic acid synthesis in liver and intestine is much higher than in tissues such as muscle.

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