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Theinformation in genes is copied and transmitted from cell to daughter cell millions of times during the life of a multicellular organism, and it survives the process essentially unchanged.'What form of molecule could be capable of suchaccurate and almost unlimited replication and also be able to direct the development of an organism and the daily life of a cell?\A/hatkind of instructions doesthe genetic information contain? How can the enormous amount of informationrequired for the development and maintenance of an organism fit within thetiny space of a cell?The answers to several of these questions began to emerge in the 1940s.Atthis time, researchers discovered, from studies in simple fungi, that geneticinformation consists primarily of instructions for making proteins. Proteins arethe macromolecules that perform most cell functions: they serve as buildingblocks for cell structures and form the enzy'rnesthat catalyze the cell's chemicalreactions (Chapter 3), they regulate gene expression (Chapter 7), and theyenable cells to communicate with each other (Chapter 15) and to move (Chapter l6).
The properties and functions of a cell are determined largely by the proteins that it is able to make. With hindsight, it is hard to imagine what other typeof instructions the genetic information could have contained.Painstaking observations of cells and embryos in the late tgth century hadled to the recognition that the hereditary information is carried on chromosomes,threadlike structures in the nucleus of a eucaryotic cell that become visible by light microscopy as the cell begins to divide (Figure 4-l). Later, as biochemical analysisbecame possible, chromosomes were found to consist of bothdeoxyribonucleic acid (DNA) and protein.
For many decades, the DNA wasthought to be merely a structural element. However, the other crucial advancemade in the 1940swas the identification of DNA as the likely carrier of geneticinformation. This breakthrough in our understanding of cells came from studiesFigure4-l Chromosomesin cells.(A)Two adjacentplantcellsphotographedthrougha light microscope.The DNAhasbeenstainedwitha fluorescentdye (DAPI)that bindsto it.The DNAis presentinchromosomes,whichbecomevisibleasdistinctstructuresin the lightstructuresmicroscopeonlywhen they becomecompact,sausage-shapedin preparationfor celldivision,asshownon the left.Thecellon the right,which is not dividing,containsidenticalchromosomes,but they cannotbeclearlydistinguishedin the light microscopeat this phasein the cell'slife(B)Schematiccycle,becausethey are in a moreextendedconformation.diagramof the outlinesof the two cellsalongwith theirchromosomes.(A,courtesyof PeterShaw.)In ThisChapterANDTHESTRUCTUREFUNCTIONOFDNA197DNA202CHROMOSOMALINAND ITSPACKAGINGFIBERTHECHROMATINOF219THEREGULATIONCHROMATINSTRUCTURE233THEGLOBALSTRUCTUREOFCHROMOSOMESEVOLVE245HOWGENOMES(A)d i v i d i n gc e t ln o n d i v i d i n gc e l l10t.196Chapter4: DNA,Chromosomes,and Genomesof inheritance in bacteria (Figure 4-2).
But as the 1950sbegan, both how proteins could be specified by instructions in the DNA and how this informationmight be copied for transmission from cell to cell seemed completely mysterious. The mystery was suddenly solved in 1953,when the structure of DNA wascorrectly predicted by Iames Watson and Francis Crick. As outlined in Chapter 1,the double-helical structure of DNA immediately solved the problem of how theinformation in this molecule might be copied, or replicated.It also provided thefirst clues as to how a molecule of DNA might use the sequenceof its subunits toencode the instructions for making proteins. Today, the fact that DNA is thegenetic material is so fundamental to biological thought that it is difficult toappreciate the enormous intellectual gap that was filled.In this chapter we begin by describing the structure of DNA. We see howdespite its chemical simplicity, the structure and chemical properties of DNAmake it ideally suited as the raw material of genes.We then consider how themany proteins in chromosomes arrange and packagethis DNA.
The packing hasto be done in an orderly fashion so that the chromosomes can be replicated andapportioned correctly between the two daughter cells at each cell division. Itmust also allow accessto chromosomal DNA for the enzymes that repair it whenit is damaged and for the specialized proteins that direct the expression of itsmany genes.We shall also see how the packaging of DNA differs along the lengthof each chromosome in eucaryotes,and how it can store a valuable record of thecell's developmental history.In the past two decades,there has been a revolution in our ability to determine the exact sequence of subunits in DNA molecules.
As a result, we nowknow the order of the 3 billion DNA subunits that provide the information forproducing a human adult from a fertilized egg, as well as the DNA sequencesofthousands of other organisms. Detailed analysesof these sequenceshave provided exciting insights into the process of evolution, and it is with this subjectthat the chapter ends.This is the first of four chapters that deal with basic genetic mechanismsthe ways in which the cell maintains, replicates, expresses,and occasionallyimproves the genetic information carried in its DNA. This chapter presents abroad overview of DNA and how it is packaged into chromosomes.
In the following chapter (Chapter 5) we discuss the mechanisms by which the cell accurately replicates and repairs DNA; we also describe how DNA sequencescan beSstrains m o o t h p a t h o g e n i cb a c t e r i u mc a u s e sD n e u m o n t aS s t r a i nc e l l sI noroovrMUTATToNtRstrainf r a c t i o n a t i o no f c e l l - rf e eextra(t into classesofp u r i f i e dm o l e c u l e sroughnonpathogenicm u r a n tD a c t e n u mCo ool i v e R s t r a i nc e l l sg r o w n i np r e s e n c eo f e i t h e r h e a t - k i l l e dS s t r a i nc e l l so r c e l l - f r e ee x t r a c to f S s t r a i nc e l l sTRANSFORMATION+5 strainS o m eR s t r a i nc e l l sa r et r a n s f o r m e dt o S s t r a i nc e l l sw, h o s ed a u g h t e r sa r e p a t h o g e n i ca n dc a u s ep n e u m o n t aC O N C L U S I OMN :o l e c u l e st h a t c a nc a r r yh e r i t a b l ei n f o r m a t i o na r epresentin 5 strain cells.(A)proteinRNADNAlipid carbohydratettttltttrlttttlmoleculestested for transformationof R strain cellsttttlttttlVVVVTocooRRSRRstrainstrainoostrainstrainC O N C L U S I OTNh: e m o l e c u l et h a tc a r r i e st h e h e r i t a b l ei n f o r m a t i o nisDNA.(B)strainFigure 4-2 The first experimentaldemonstrationthat DNA is the geneticmaterial.Theseexperiments,carriedoutin the 1940s,showedthat addingpurifiedDNAto a bacteriumchangeditspropertiesand that this changewasfaithfullypassedon to subsequentgenerations.Two closelyrelatedstrainsofpneumoniaethe bacteriumStreptococcusdifferfrom eachother in both theirappearanceunderthe microscopeandtheir pathogenicity.One strainappearssmooth(5)and causesdeathwheninjectedinto mice,and the otherappearsrough(R)and is nonlethal.(A)An initialexperimentshowsthat a substancepresentin the S straincanchange(ortransform)the R straininto the S strainand that this changeis inheritedbygenerationssubsequentof bacteria.(B)Thisexperiment,in whichthe R strainhasbeenincubatedwith variousclassesof biologicalmoleculespurifiedfrom theS strain,identifiesthe substanceas DNA.THESTRUCTUREAND FUNCTIONOF DNArearranged through the process of genetic recombination.
Gene expressionthe process through which the information encoded in DNA is interpreted bythe cell to guide the synthesis of proteins-is the main topic of Chapter 6. InChapter 7, we describe how this gene expression is controlled by the cell toensure that each of the many thousands of proteins and RNA moleculesencrlpted in its DNA are manufactured only at the proper time and place in thelife of the cell.THESTRUCTUREANDFUNCTIONOFDNABiologists in the 1940s had difficulty in conceiving how DNA could be thegenetic material because of the apparent simplicity of its chemistry. DNA wasknown to be a long poll.rner composed of only four types of subunits, whichresemble one another chemically. Early in the 1950s,DNA was examined by xray diffraction analysis, a technique for determining the three-dimensionalatomic structure of a molecule (discussedin Chapter 8).
The early x-ray diffraction results indicated that DNA was composed of two strands of the polymerwound into a helix. The observation that DNA was double-stranded was of crucial significance and provided one of the major clues that led to theWatson-Crick model for DNA structure.
But onlywhen this model was proposedin 1953 did DNAs potential for replication and information encoding becomeapparent. In this section we examine the structure of the DNA molecule andexplain in general terms how it is able to store hereditary information.A DNAMoleculeConsistsof TwoComplementaryChainsofNucleotidesA deoxyribonucleic acid (DNA) molecule consists of two long polynucleotidechains composed of four types of nucleotide subunits. Each of these chains isknornm as a D.ly'Achain, or a DNA strand. Hydrogen bondsbetween the base portions of the nucleotides hold the two chains together (Figure 4-3).
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