H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003), страница 5

The genes that carry instructions for making proteins commonly contain two parts:a coding region that specifies the amino acid sequence of aprotein and a regulatory region that controls when and inwhich 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 copiedinto a single-stranded ribonucleic acid (RNA) version of thedouble-stranded DNA.

A large enzyme, RNA polymerase,catalyzes the linkage of nucleotides into a RNA chain usingDNA as a template. In eukaryotic cells, the initial RNAproduct is processed into a smaller messenger RNA (mRNA)molecule, which moves to the cytoplasm. Here the ribosome,an enormously complex molecular machine composed ofboth RNA and protein, carries out the second process, calledtranslation. During translation, the ribosome assembles andlinks together amino acids in the precise order dictated by themRNA sequence according to the nearly universal geneticcode.

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 theirgenes can be transcribed. For instance, nearly all the cells inour bodies contain the full set of human genes, but in eachcell type only some of these genes are active, or turned on,and used to make proteins. That’s why liver cells producesome proteins that are not produced by kidney cells, and viceversa.

Moreover, many cells can respond to external signalsor changes in external conditions by turning specific genes onor off, thereby adapting their repertoire of proteins to meetcurrent needs. Such control of gene activity depends onDNA-binding proteins called transcription factors, whichbind to DNA and act as switches, either activating or repressing transcription of particular genes (Chapter 11).Transcription factors are shaped so precisely that they areable to bind preferentially to the regulatory regions of just afew 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 DNAcontaining 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 occurin the DNA of a cell, assuring the specificity of gene activationand repression. Multiple copies of one type of transcriptionfactor can coordinately regulate a set of genes if binding sitesfor that factor exist near each gene in the set.

Transcriptionfactors often work as multiprotein complexes, with morethan one protein contributing its own DNA-binding specificity to selecting the regulated genes. In complex organisms,111ActivationDNAStart2Transcriptionpre-mRNANucleus3ProcessingmRNAProtein4CytosolTranslationTranscriptionfactorRNApolymeraseRibosomeTranscribed region of DNANontranscribed region of DNAProtein-coding region of RNANoncoding region of RNAAmino acid chain▲ FIGURE 1-11 The coded information in DNA is convertedinto the amino acid sequences of proteins by a multistepprocess. Step 1 : Transcription factors bind to the regulatoryregions of the specific genes they control and activate them.Step 2 : Following assembly of a multiprotein initiation complexbound to the DNA, RNA polymerase begins transcription of anactivated gene at a specific location, the start site.

Thepolymerase moves along the DNA linking nucleotides into asingle-stranded pre-mRNA transcript using one of the DNAstrands as a template. Step 3 : The transcript is processed toremove noncoding sequences. Step 4 : In a eukaryotic cell, themature messenger RNA (mRNA) moves to the cytoplasm, whereit is bound by ribosomes that read its sequence and assemble aprotein by chemically linking amino acids into a linear chain.hundreds of different transcription factors are employed toform an exquisite control system that activates the right genesin the right cells at the right times.The Genome Is Packaged into Chromosomesand Replicated During Cell DivisionMost of the DNA in eukaryotic cells is located in the nucleus,extensively folded into the familiar structures we know aschromosomes (Chapter 10).

Each chromosome contains a single linear DNA molecule associated with certain proteins. Inprokaryotic cells, most or all of the genetic information resides12CHAPTER 1 • Life Begins with Cellsin a single circular DNA molecule about a millimeter in length;this molecule lies, folded back on itself many times, in the central region of the cell (see Figure 1-2a).

The genome of an organism comprises its entire complement of DNA. With theexception of eggs and sperm, every normal human cell has 46chromosomes (Figure 1-12). Half of these, and thus half of thegenes, can be traced back to Mom; the other half, to Dad.Every time a cell divides, a large multiprotein replicationmachine, the replisome, separates the two strands of doublehelical DNA in the chromosomes and uses each strand as atemplate to assemble nucleotides into a new complementarystrand (see Figure 1-10). The outcome is a pair of double helices, each identical to the original.

DNA polymerase, whichis responsible for linking nucleotides into a DNA strand, andthe many other components of the replisome are described inChapter 4. The molecular design of DNA and the remarkableproperties of the replisome assure rapid, highly accurate copying. Many DNA polymerase molecules work in concert, eachone copying part of a chromosome. The entire genome of fruitflies, about 1.2 108 nucleotides long, can be copied in threeminutes! Because of the accuracy of DNA replication, nearlyall the cells in our bodies carry the same genetic instructions,and we can inherit Mom’s brown hair and Dad’s blue eyes.A rather dramatic example of gene control involves inactivation of an entire chromosome in human females.Women have two X chromosomes, whereas men have one▲ FIGURE 1-12 Chromosomes can be “painted” for easyidentification.

A normal human has 23 pairs of morphologicallydistinct chromosomes; one member of each pair is inheritedfrom the mother and the other member from the father. (Left) Achromosome spread from a human body cell midway throughmitosis, when the chromosomes are fully condensed. Thispreparation was treated with fluorescent-labeled stainingreagents that allow each of the 22 pairs and the X and YX chromosome and one Y chromosome, which has different genes than the X chromosome. Yet the genes on the Xchromosome must, for the most part, be equally active in female cells (XX) and male cells (XY).

To achieve this balance,one of the X chromosomes in female cells is chemically modified and condensed into a very small mass called a Barrbody, which is inactive and never transcribed.Surprisingly, we inherit a small amount of genetic material entirely and uniquely from our mothers. This is the circular DNA present in mitochondria, the organelles ineukaryotic cells that synthesize ATP using the energy releasedby the breakdown of nutrients. Mitochondria contain multiple copies of their own DNA genomes, which code forsome of the mitochondrial proteins (Chapter 10). Becauseeach human inherits mitochondrial DNA only from his orher mother (it comes with the egg but not the sperm), the distinctive features of a particular mitochondrial DNA can beused to trace maternal history. Chloroplasts, the organellesthat carry out photosynthesis in plants, also have their owncircular genomes.Mutations May Be Good, Bad, or IndifferentMistakes occasionally do occur spontaneously during DNAreplication, causing changes in the sequence of nucleotides.Such changes, or mutations, also can arise from radiationchromosomes to appear in a different color when viewed in afluorescence microscope.

This technique of multiplexfluorescence in situ hybridization (M-FISH) sometimes is calledchromosome painting (Chapter 10). (Right) Chromosomes fromthe preparation on the left arranged in pairs in descending orderof size, an array called a karyotype. The presence of X and Ychromosomes identifies the sex of the individual as male.[Courtesy of M. R. Speicher.]1.3 • The Work of Cellsthat causes damage to the nucleotide chain or from chemical poisons, such as those in cigarette smoke, that lead to errors during the DNA-copying process (Chapter 23).Mutations come in various forms: a simple swap of one nucleotide for another; the deletion, insertion, or inversion ofone to millions of nucleotides in the DNA of one chromosome; and translocation of a stretch of DNA from one chromosome to another.In sexually reproducing animals like ourselves, mutationscan be inherited only if they are present in cells that potentially contribute to the formation of offspring.

Such germ-linecells include eggs, sperm, and their precursor cells. Body cellsthat do not contribute to offspring are called somatic cells.Mutations that occur in these cells never are inherited, although they may contribute to the onset of cancer. Plants havea less distinct division between somatic and germ-line cells,since many plant cells can function in both capacities.Mutated genes that encode altered proteins or that cannot be controlled properly cause numerous inherited diseases. For example, sickle cell disease is attributable to asingle nucleotide substitution in the hemoglobin gene, whichencodes the protein that carries oxygen in red blood cells.The single amino acid change caused by the sickle cell mutation reduces the ability of red blood cells to carry oxygenfrom the lungs to the tissues.