For Making Proteins at the Right Time and Place

The information about how, when, and where to produce each kind of protein is carried in the genetic material, a polymer called deoxyribonucleic acid (DNA). The three-dimensional structure of DNA consists of two long helical strands that are coiled around a common axis, forming a double helix. DNA strands are composed of monomers called nucleotides; these often are referred to as bases because their structures contain cyclic organic bases (Chapter 4).

Four different nucleotides, abbreviated A, T, C, and G, are joined end to end in a DNA strand, with the base parts projecting out from the helical backbone of the strand. Each DNA double helix has a simple construction: wherever there is an A in one strand there is a T in the other, and each C is matched with a G (Figure 1-10). This complementary matching of the two strands is so strong that if complementary strands are separated, they will spontaneously zip back together in the right salt and temperature conditions. Such hybridization is extremely useful for detecting one strand using the other. For example, if one strand is purified and attached to a piece of paper, soaking the paper in a solution containing the other complementary strand will lead to zippering, as templates to produce complementary strands. The outcome is two copies of the original double helix, each containing one of the original strands and one new daughter (complementary) strand.

even if the solution also contains many other DNA strands that do not match.

The genetic information carried by DNA resides in its sequence, the linear order of nucleotides along a strand. The information-bearing portion of DNA is divided into discrete functional units, the genes, which typically are 5000 to 100,000 nucleotides long. Most bacteria have a few thousand genes; humans, about 40,000. The genes that carry instructions for making proteins commonly contain two parts: a coding region that specifies the amino acid sequence of a protein and a regulatory region that controls when and in which cells the protein is made.

Cells use two processes in series to convert the coded information in DNA into proteins (Figure 1-11). In the first, called transcription, the coding region of a gene is copied into a single-stranded ribonucleic acid (RNA) version of the double-stranded DNA. A large enzyme, RNA polymerase, catalyzes the linkage of nucleotides into a RNA chain using DNA as a template. In eukaryotic cells, the initial RNA product is processed into a smaller messenger RNA (mRNA) molecule, which moves to the cytoplasm. Here the ribosome, an enormously complex molecular machine composed of both RNA and protein, carries out the second process, called translation. During translation, the ribosome assembles and links together amino acids in the precise order dictated by the mRNA sequence according to the nearly universal genetic code. We examine the cell components that carry out transcription and translation in detail in Chapter 4.

All organisms have ways to control when and where their genes can be transcribed. For instance, nearly all the cells in our bodies contain the full set of human genes, but in each cell type only some of these genes are active, or turned on, and used to make proteins. That's why liver cells produce some proteins that are not produced by kidney cells, and vice versa. Moreover, many cells can respond to external signals or changes in external conditions by turning specific genes on or off, thereby adapting their repertoire of proteins to meet current needs. Such control of gene activity depends on DNA-binding proteins called transcription factors, which bind to DNA and act as switches, either activating or repressing transcription of particular genes (Chapter 11).

Transcription factors are shaped so precisely that they are able to bind preferentially to the regulatory regions of just a few genes out of the thousands present in a cell's DNA. Typically a DNA-binding protein will recognize short DNA sequences about 6-12 base pairs long. A segment of DNA containing 10 base pairs can have 410 possible sequences (1,048,576) since each position can be any of four nucleotides. Only a few copies of each such sequence will occur in the DNA of a cell, assuring the specificity of gene activation and repression. Multiple copies of one type of transcription factor can coordinately regulate a set of genes if binding sites for that factor exist near each gene in the set. Transcription factors often work as multiprotein complexes, with more than one protein contributing its own DNA-binding specificity to selecting the regulated genes. In complex organisms, o ynoQowwwwwmmmmmmososeK.

Activation DNA I

Transcription

Processing pre-mRNA

Nucleus mRNA

Translation mRNA

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