B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 67
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The puzzle was suddenly solved in 1953,when James Watson and Francis Crick derived the mechanism from their modelof DNA structure. As outlined in Chapter 1, the determination of the double-helical structure of DNA immediately solved the problem of how the informationin this molecule might be copied, or replicated. It also provided the first clues asto how a molecule of DNA might use the sequence of its subunits to encode theinstructions for making proteins.
Today, the fact that DNA is the genetic materialis so fundamental to biological thought that it is difficult to appreciate the enormous intellectual gap that was filled by this breakthrough discovery.We begin this chapter by describing the structure of DNA. We see how, despiteits chemical simplicity, the structure and chemical properties of DNA make itideally suited as the raw material of genes. We then consider how the many proteins in chromosomes arrange and package this DNA. The packing has to be donein an orderly fashion so that the chromosomes can be replicated and apportionedcorrectly between the two daughter cells at each cell division. And it must alsoallow access to chromosomal DNA, both for the enzymes that repair DNA damageand for the specialized proteins that direct the expression of its many genes.In the past two decades, there has been a revolution in our ability to determine the exact order of subunits in DNA molecules.
As a result, we now know theS strainsmooth pathogenic bacteriumcauses pneumoniaFRACTIONATION OF CELL-FREEEXTRACT INTO CLASSES OFPURIFIED MOLECULESrough nonpathogenicmutant bacteriumlive R strain cells grown inpresence of either heat-killedS strain cells or cell-freeextract of S strain cellsRNAproteinDNAlipid carbohydratemolecules tested for transformation of R strain cellsTRANSFORMATIONS strainsome R strain cells aretransformed to S straincells, whose daughtersare pathogenic andcause pneumoniaCONCLUSION: Molecules that cancarry heritable information arepresent in S strain cells.(A)nondividing cell(B)10 μmMBoC6 m4.01/4.01S strain cellsRANDOM MUTATIONR straindividing cellRstrainRstrainSstrainRstrainCONCLUSION: The molecule thatcarries the heritable informationis DNA.(B)RstrainFigure 4–2 The first experimentaldemonstration that DNA is the geneticmaterial.
These experiments, carried outin the 1920s (A) and 1940s (B), showedthat adding purified DNA to a bacteriumchanged the bacterium’s properties andthat this change was faithfully passedon to subsequent generations. Twoclosely related strains of the bacteriumStreptococcus pneumoniae differ fromeach other in both their appearance underthe microscope and their pathogenicity.One strain appears smooth (S) and causesdeath when injected into mice, and theother appears rough (R) and is nonlethal.(A) An initial experiment shows that somesubstance present in the S strain canchange (or transform) the R strain into theS strain and that this change is inherited bysubsequent generations of bacteria.(B) This experiment, in which the R strainhas been incubated with various classesof biological molecules purified from theS strain, identifies the active substanceas DNA.THE STRUCTURE AND FUNCTION OF DNAsequence of the 3.2 billion nucleotide pairs that provide the information for producing a human adult from a fertilized egg, as well as having the DNA sequencesfor thousands of other organisms.
Detailed analyses of these sequences are providing exciting insights into the process of evolution, and it is with this subject thatthe chapter ends.This is the first of four chapters that deal with basic genetic mechanisms—theways in which the cell maintains, replicates, and expresses the genetic information carried in its DNA. In the next chapter (Chapter 5), we shall discuss the mechanisms by which the cell accurately replicates and repairs DNA; we also describehow DNA sequences can be rearranged through the process of genetic recombination.
Gene expression—the process through which the information encoded inDNA is interpreted by the cell to guide the synthesis of proteins—is the main topicof Chapter 6. In Chapter 7, we describe how this gene expression is controlled bythe cell to ensure that each of the many thousands of proteins and RNA moleculesencrypted in its DNA is manufactured only at the proper time and place in the lifeof a cell.THE STRUCTURE AND FUNCTION OF DNABiologists in the 1940s had difficulty in conceiving how DNA could be the geneticmaterial. The molecule seemed too simple: a long polymer composed of only fourtypes of nucleotide subunits, which resemble one another chemically.
Early in the1950s, DNA was examined by x-ray diffraction analysis, a technique for determining the three-dimensional atomic structure of a molecule (discussed in Chapter8). The early x-ray diffraction results indicated that DNA was composed of twostrands of the polymer wound into a helix.
The observation that DNA was double-stranded provided one of the major clues that led to the Watson–Crick modelfor DNA structure that, as soon as it was proposed in 1953, made DNA’s potentialfor replication and information storage apparent.A DNA Molecule Consists of Two Complementary Chains ofNucleotidesA deoxyribonucleic acid (DNA) molecule consists of two long polynucleotidechains composed of four types of nucleotide subunits.
Each of these chains isknown as a DNA chain, or a DNA strand. The chains run antiparallel to each other,and hydrogen bonds between the base portions of the nucleotides hold the twochains together (Figure 4–3). As we saw in Chapter 2 (Panel 2–6, pp. 100–101),nucleotides are composed of a five-carbon sugar to which are attached one ormore phosphate groups and a nitrogen-containing base.
In the case of the nucleotides in DNA, the sugar is deoxyribose attached to a single phosphate group(hence the name deoxyribonucleic acid), and the base may be either adenine (A),cytosine (C), guanine (G), or thymine (T). The nucleotides are covalently linkedtogether in a chain through the sugars and phosphates, which thus form a “backbone” of alternating sugar–phosphate–sugar–phosphate. Because only the basediffers in each of the four types of nucleotide subunit, each polynucleotide chainin DNA is analogous to a sugar-phosphate necklace (the backbone), from whichhang the four types of beads (the bases A, C, G, and T). These same symbols (A,C, G, and T) are commonly used to denote either the four bases or the four entirenucleotides—that is, the bases with their attached sugar and phosphate groups.The way in which the nucleotides are linked together gives a DNA strand achemical polarity.
If we think of each sugar as a block with a protruding knob (the5ʹ phosphate) on one side and a hole (the 3ʹ hydroxyl) on the other (see Figure4–3), each completed chain, formed by interlocking knobs with holes, will haveall of its subunits lined up in the same orientation. Moreover, the two ends of thechain will be easily distinguishable, as one has a hole (the 3ʹ hydroxyl) and theother a knob (the 5ʹ phosphate) at its terminus.
This polarity in a DNA chain isindicated by referring to one end as the 3ʹ end and the other as the 5ʹ end, namesderived from the orientation of the deoxyribose sugar. With respect to DNA’s175176Chapter 4: DNA, Chromosomes, and Genomesbuilding blocks of DNADNA strandsugarphosphate+sugarphosphate5′Gbase(guanine)3′CTAATATC3′CGCTACG5′CGTAATAGGA5′DNA double helix5′GTAnucleotidedouble-stranded DNA3′CGGGsugar-phosphatebackboneCCGCGACAT5′3′GT3′hydrogen-bondedbase pairsinformation-carrying capacity,the chain of nucleotides in a DNA strand, beingMBoC6 m4.03/4.03both directional and linear, can be read in much the same way as the letters onthis page.The three-dimensional structure of DNA—the DNA double helix—arises fromthe chemical and structural features of its two polynucleotide chains.
Becausethese two chains are held together by hydrogen-bonding between the bases onthe different strands, all the bases are on the inside of the double helix, and thesugar-phosphate backbones are on the outside (see Figure 4–3). In each case, abulkier two-ring base (a purine; see Panel 2–6, pp.
100–101) is paired with a single-ring base (a pyrimidine): A always pairs with T, and G with C (Figure 4–4).This complementary base-pairing enables the base pairs to be packed in the energetically most favorable arrangement in the interior of the double helix. In thisarrangement, each base pair is of similar width, thus holding the sugar-phosphatebackbones a constant distance apart along the DNA molecule. To maximize theefficiency of base-pair packing, the two sugar-phosphate backbones wind aroundeach other to form a right-handed double helix, with one complete turn every tenbase pairs (Figure 4–5).The members of each base pair can fit together within the double helix onlyif the two strands of the helix are antiparallel—that is, only if the polarity of onestrand is oriented opposite to that of the other strand (see Figures 4–3 and 4–4).A consequence of DNA’s structure and base-pairing requirements is that eachstrand of a DNA molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand.Figure 4–3 DNA and its building blocks.DNA is made of four types of nucleotides,which are linked covalently into apolynucleotide chain (a DNA strand) witha sugar-phosphate backbone from whichthe bases (A, C, G, and T) extend.
A DNAmolecule is composed of two antiparallelDNA strands held together by hydrogenbonds between the paired bases. Thearrowheads at the ends of the DNA strandsindicate the polarities of the two strands. Inthe diagram at the bottom left of the figure,the DNA molecule is shown straightenedout; in reality, it is twisted into a doublehelix, as shown on the right. For details,see Figure 4–5 and Movie 4.1.THE STRUCTURE AND FUNCTION OF DNA177Figure 4–4 Complementary base pairsin the DNA double helix. The shapesand chemical structures of the basesallow hydrogen bonds to form efficientlyonly between A and T and between Gand C, because atoms that are able toform hydrogen bonds (see Panel 2–3,pp.
94–95) can then be brought closetogether without distorting the double helix.As indicated, two hydrogen bonds formbetween A and T, while three form betweenG and C. The bases can pair in this wayonly if the two polynucleotide chains thatcontain them are antiparallel to each other.3′5′HNCCHCNHOHNNHguanine3′CHNcytosineHhydrogenbondHCCOHCNHCCNNCCGCCCH3thymineHNNCOHHCCNsugar–phosphatebackboneTNHCNadenineNCACNO5′1 nm(A)The Structure of DNA Provides a Mechanism for HeredityThe discovery of the structure of DNA immediately suggested answers to the twomost fundamental questions about heredity. First, how could the information tom4.04/4.04specify an organism be carriedMBoC6in a chemicalform? And second, how could thisinformation be duplicated and copied from generation to generation?The answer to the first question came from the realization that DNA is a linearpolymer of four different kinds of monomer, strung out in a defined sequence likethe letters of a document written in an alphabetic script.The answer to the second question came from the double-stranded nature ofthe structure: because each strand of DNA contains a sequence of nucleotidesthat is exactly complementary to the nucleotide sequence of its partner strand,each strand can act as a template, or mold, for the synthesis of a new complementary strand.
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