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You are watching: A sequence of sugars, phosphates, and nitrogenous organic bases

Lodish H, Berk A, Zipursky SL, et al. Molecular cell Biology. 4th edition. New York: W. H. Freeman; 2000.


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DNA and also RNA have good chemical similarities. In their primarystructures both are linear polymers (multiple chemical units) composed of monomers (single chemistry units), called nucleotides. To move RNAs variety inlength from less than one hundreds to many thousands the nucleotides. To move DNAmolecules deserve to be as lengthy as numerous hundred million nucleotides. These big DNAunits in association with proteins deserve to be stained through dyes and also visualized in thelight microscopic lense as chromosomes.


Polymerization the Nucleotides develops Nucleic Acids

DNA and RNA each consists of only four various nucleotides. Every nucleotideshave a usual structure: a phosphate group connected by aphosphoester bond to a pentose (a five-carbon street molecule)that subsequently is attached to an organic base (Figure 4-1a). In RNA, the pentose isribose; in DNA, that is deoxyribose (Figure 4-1b). The just other distinction inthe nucleotides of DNA and also RNA is that among the 4 organic bases differsbetween the 2 polymers. The bases adenine, guanine, and cytosine are found inboth DNA and also RNA; thymine is found only in DNA, and also uracil is uncovered only in RNA.The bases are frequently abbreviated A, G, C, T, and U, respectively. For conveniencethe solitary letters are likewise used when lengthy sequences of nucleotides space writtenout.


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Figure 4-1

All Nucleotides have actually a usual structure. (a) Chemical structure of adenosine 5′-monophosphate (AMP),a nucleotide the is present in RNA. Every nucleotides room composed ofa phosphate moiety, containing increase to three phosphate groups, linkedto the (more...)


The base components of nucleic acids are heterocyclic compounds through the ringscontaining nitrogen and carbon. Adenine and guanine space purines, which contain a pair offused rings; cytosine, thymine, and also uracil room pyrimidines, i m sorry contain a single ring (Figure 4-2). The acidic character ofnucleotides is as result of the existence of phosphate, which dissociates at the pHfound within cells, freeing hydrogen ions and leaving the phosphate negativelycharged (see number 2-22). Due to the fact that thesecharges attract proteins, many nucleic acids in cell are connected withproteins. In nucleotides, the 1′ carbon atom the the sugar (ribose ordeoxyribose) is attached to the nitrogen at place 9 the a purine(N9) or at place 1 the a pyrimidine (N1).


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Figure 4-2

The chemical structures of the major bases in nucleicacids. In nucleic acids and also nucleotides, nitrogen 9 that purines and also nitrogen1 the pyrimidines (red) space bonded to the 1′ carbon ofribose or deoxyribose.


Cells and also extracellular fluids in biology contain little concentrations of nucleosides, combinations of a baseand a sugar without a phosphate. Nucleotides room nucleosides that have one, two,or 3 phosphate teams esterified at the 5′ hydroxyl.Nucleoside monophosphates have actually a single esterifiedphosphate (see number 4-1a),diphosphates save on computer a prophosphate group


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and triphosphates have a 3rd phosphate. Table 4-1 lists the names of the nucleosides andnucleotides in main point acids and also the various develops of nucleoside phosphates. Aswe will check out later, the nucleoside triphosphates are used in the synthesis ofnucleic acids. However, this compounds also serve plenty of other features in thecell: ATP, for example, is the most widely used energy carrier in the cell (seeFigure 2-25), and also GTP dram crucialroles in intracellular signaling and also acts together an energy reservoir, particularlyin protein synthesis.


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When nucleotides polymerize to kind nucleic acids, the hydroxyl group attached tothe 3′ carbon of a sugar of one nucleotide develops an ester bond come thephosphate of one more nucleotide, eliminating a molecule that water:


This condensation reaction is similar to that in i beg your pardon a peptide link is formedbetween two amino mountain (Chapter3). For this reason a solitary nucleic mountain strand is a phosphate-pentose polymer (apolyester) with purine and pyrimidine bases together side groups. The links betweenthe nucleotides are dubbed phosphodiesterbonds. Like a polypeptide, a nucleic acid strand has an end-to-endchemical orientation: the 5′ end hasa complimentary hydroxyl or phosphate group on the 5′ carbon that its terminalsugar; the 3′ finish has a freehydroxyl group on the 3′ carbon the its terminal street (Figure 4-3). This directionality, add to thefact that synthesis proceeds 5′ to 3′, has offered rise come theconvention the polynucleotide sequences room written and also read in the5′ → 3′ direction (from left come right); forexample, the succession AUG is assumed to it is in (5′)AUG(3′).(Although, strict speaking, the letters A, G, C, T, and also U stand for bases,they are likewise often offered in diagrams to represent the totality nucleotidescontaining this bases.) The 5′ → 3′directionality of a nucleic mountain strand is very important home ofthe molecule.


Figure 4-3

Alternative means of representing nucleic acid chains, in thiscase a single strand of DNA containing only three bases: cytosine(C), adenin (A), and also guanine (G). (a) Chemical structure of the trinucleotide CAG. Keep in mind the freehydroxyl team at the 3′ (more...)


The linear sequence the nucleotides connected by phosphodiester binding constitutes theprimary structure of main point acids. As we comment on in the next section,polynucleotides have the right to twist and also fold right into three-dimensional conformationsstabilized by noncovalent bonds; in this respect, they are comparable topolypeptides. Back the major structures the DNA and also RNA room generallysimilar, their conformations are quite different. Unequal RNA, which commonlyexists as a single polynucleotide chain, or strand, DNA consists of two intertwinedpolynucleotide strands. This structural distinction is an important to the differentfunctions that the two species of main point acids.


Native DNA Is a dual Helix of complementary Antiparallel Chains

The modern era of molecule biology began in 1953 once James D. Watson andFrancis H. C. Crick proposed properly the double-helical framework of DNA,based ~ above the analysis of x-ray diffraction trends coupled with cautious modelbuilding. A closer look in ~ the “thread that life,” together the DNAmolecule is periodically called, mirrors why the discovery of its basic structuresuggests that is function.

DNA consists of two linked polynucleotide strands the windtogether through room to form a structure often describedas a dual helix. The 2 sugar-phosphate backbones room on theoutside the the double helix, and the bases project into the interior. Theadjoining bases in every strand ridge on top of one one more in parallel planes(Figure 4-4a). The orientation that thetwo strands is antiparallel; the is, your 5′ →3′ directions room opposite. The strands are organized in specific registerby a consistent base-pairing between the 2 strands: A is paired through T throughtwo hydrogen bonds; G is paired through C through 3 hydrogen bond (Figure 4-4b). This base-paircomplementarity is a consequence of the size, shape, and also chemicalcomposition the the bases. The visibility of countless such hydrogen bonds in aDNA molecule contributes considerably to the stability of the twin helix.Hydrophobic and also van der Waals interactions between the stacked surrounding basepairs also contribute to the security of the DNA structure.


Figure 4-4

Two depictions of contacts within the DNA doublehelix. (a) Space-filling version of B DNA, the most common kind of DNA incells. The sugar and also phosphate residues (gray) in every strand formthe backbone, i beg your pardon is traced through a red line, mirroring the helicaltwist (more...)


To preserve the geometry of the double-helical structure shown in figure 4-4a, a larger purine (A or G) mustpair with a smaller pyrimidine (C or T). In organic DNA, A practically alwayshydrogen bonds v T and also G v C, forming A·T and also G·Cbase pairs often referred to as Watson-Crick base pairs. Twopolynucleotide strands, or areas thereof, in which every the nucleotides formsuch base pairs are stated to be complementary. However, in theory and in fabricated DNAs otherinteractions have the right to occur. For example, a guanine (a purine) could theoreticallyform hydrogen bonds with a thymine (a pyrimidine), causing only a minordistortion in the helix. The space available in the helix additionally would allowpairing in between the two pyrimidines cytosine and also thymine. Return thenonstandard G·T and also C·T basic pairs are normally not foundin DNA, G·U basic pairs room quite typical in double-helical regionsthat kind within otherwise single-stranded RNA.

Two polynucleotide strands can, in principle, form either a right-handed or aleft-handed helix (Figure 4-5). Becausethe geometry the the sugar-phosphate backbone is more compatible with the former,natural DNA is a right-handed helix. The x-ray diffraction pattern of DNAindicates that the stack bases are routinely spaced 0.34 nm apart follow me thehelix axis. The helix provides a finish turn every 3.4 nm; thus there room about10 pairs per turn. This is described as the B type of DNA,the normal form present in most DNA follow me in cells (Figure 4-6a). ~ above the outside of B-form DNA, the spacesbetween the intertwined strands form two helical grooves of different widthsdescribed as the significant groove and also the minorgroove (see number 4-4a). Consequently,part of each base is easily accessible from exterior the helix come both small and largemolecules that bind to the DNA by contacting chemical groups within the grooves.These two binding surface of the DNA molecule are offered by different classes ofDNA-binding proteins.


Figure 4-5

Two feasible helical forms of DNA space mirror pictures of eachother. The geometry of the sugar-phosphate backbone of DNA reasons naturalDNA to it is in right-handed. (Right-handed andleft-handed are defined by convention.)


Figure 4-6

Models of miscellaneous DNA frameworks that are recognized to exist. The sugar-phosphate backbone of each chain is on the exterior in allstructures (one red and one blue) v the bases (silver) orientedinward. Side views are presented at the top, and views follow me the (more...)


In enhancement to the significant B form of DNA, three added structures have beendescribed. In really low humidity, the crystallographic structure of B DNA changesto the A form; RNA-DNA and RNA-RNA helices likewise exist in thisform. The A type is an ext compact than the B form, having 11 bases every turn, andthe stack bases room tilted (Figure4-6b). Brief DNA molecules created of alternating purine-pyrimidinenucleotides (especially Gs and also Cs) adopt an alternate left-handedconfiguration rather of the typical right-handed helix. This framework is calledZ DNA since the bases seem come zigzag as soon as viewed indigenous theside (Figure 4-6c). It is entirelypossible that both A-form and also Z-form follow me of DNA exist in cells.

Finally, a triple-stranded DNA framework can additionally exist at least in the testtube, and also possibly throughout recombination and DNA repair. Because that example, whensynthetic polymers the poly(A) and also polydeoxy(U) room mixed, a three-strandedstructure is formed (Figure 4-6d).Further, lengthy homopolymeric follow me of DNA composed of C and T residues in onestrand and A and also G residues in the other have the right to be target by short matchinglengths of poly(C+T). The fabricated oligonucleotide deserve to insert together athird strand, binding in a sequence-specific path by so-calledHoogsteen basic pairs. Particular cleavage the the DNA at thesite whereby the triple helix ends can be accomplished by attaching a chemicalcleaving agent (e.g., Fe2+-EDTA) come the shortoligodeoxynucleotide that renders up the 3rd strand. Such reactions may beuseful in researching site-specific DNA damages in cells.

By far the many important adjustments in typical B-form DNA come about as aresult the protein binding to specific DNA sequences. Back the multitude ofhydrogen and hydrophobic bonds between the polynucleotide strands providestability to DNA, the twin helix is somewhat flexible around its lengthy axis.Unlike the α helix in protein (see figure 3-6), there room no hydrogen bonds between successive residuesin a DNA strand. This prop- erty permits DNA to bend once complexed through aDNA-binding protein. Crystallographic analyses of proteins bound come particularregions the DNA have actually conclusively demonstrated departures indigenous the typical B-DNAstructure in protein-DNA complexes. Two examples of DNA deformed by call withproteins are displayed in figure 4-7. Thespecific DNA-protein contact that take place in this tightly bound complexes havethe capacity both to untwist the DNA and to bend the axis that the helix. AlthoughDNA in cells likely exists in the B kind most of the time, particular regionsbound to protein plainly depart native the conventional conformation.


Figure 4-7

Bending of OF DNA resulting from protein binding. (a) A straight DNA (left) is presented binding a repressorprotein encoded by bacter 434 (center); theresulting bend in the DNA (right) is conveniently seen bycomparison with the direct molecule. Binding (more...)


DNA deserve to Undergo Reversible Strand Separation

In DNA replication and in the copy of RNA indigenous DNA, the strands that the helixmust different at the very least temporarily. As we talk about later, during DNA synthesistwo brand-new strands space made (one duplicated from each of the original strands),resulting in two double helices the same with the initial one. In the situation ofcopying the DNA layout to do RNA, the RNA is released and also the 2 DNAstrands reassociate v each other.

The unwinding and separation that DNA strands, described as denaturation, or“melting,” have the right to be induced experimentally. For example, if asolution that DNA is heated, the thermal energy increases molecule motion,eventually breaking the hydrogen bonds and also other forces that stabilize thedouble helix, and the strands different (Figure4-8). This melting of DNA alters its absorb of ultraviolet (UV)light (in the 260-nm range), which is routinely supplied to measure up DNAconcentration due to the fact that of the high absorbance that UV irradiate by nucleic mountain bases.Native double-stranded DNA absorbs around one-half as much light in ~ 260 nm asdoes the identical amount of single-stranded DNA (Figure 4-9a). Thus, as DNA denatures, its absorption of UVlight increases. Near the denaturation temperature, a little increase intemperature causes an abrupt, close to simultaneous, lose of the multiple, weak,cooperative interactions holding the 2 strands together, so that denaturationrapidly occurs throughout the whole length that the DNA.


Figure 4-9

Light absorption and also temperature in DNA denaturation. (a) melting of doubled-stranded DNA have the right to be monitored through theabsorption the ultraviolet light at 260 nm. As areas ofdouble-stranded DNA unpair, the absorption of light by those regionsincreases practically (more...)


The melting temperature, Tm, in ~ which the strands ofDNA will separate relies on numerous factors. Molecules the contain a greaterproportion that G·C pairs require greater temperatures come denaturebecause the three hydrogen bond in G·C pairs make them an ext stablethan A·T pairs v two hydrogen bonds (see figure 4-4b). Indeed, the portion of G·Cbase bag in a DNA sample have the right to be estimated from itsTm (Figure4-9b). In enhancement to heat, services of short ion concentrationdestabilize the twin helix, leading to it come melt at reduced temperatures. DNA isalso denatured by exposure to other agents that destabilize hydrogen bonds, suchas alkaline solutions and concentrated options of formamide or urea:


The single-stranded DNA molecule that result from denaturation type random coilswithout a constant structure. Lowering the temperature or boosting the ionconcentration causes the 2 complementary strands come reassociate right into a perfectdouble helix (see figure 4-8). The extentof such renaturation is dependence on time, the DNAconcentration, and also the ionic contents of the solution. 2 DNA strands notrelated in succession will continue to be as arbitrarily coils and also will no renature and, mostimportant, will certainly not substantially inhibit safety DNA companion strands fromfinding every other. Denaturation and also renaturation of DNA room the basis ofnucleic mountain hybridization, apowerful technique used to study the relatedness of 2 DNA samples and also todetect and also isolate specific DNA molecule in a mixture include numerousdifferent DNA sequences (Chapter7).


Many DNA Molecules space Circular

All prokaryotic genomic DNAs and many famous DNAs are circular molecules. CircularDNA molecules also occur in mitochondria, i m sorry are current in almost alleukaryotic cells, and in chloroplasts, which are present in plants and someunicellular eukaryotes.

Each the the two strands in a one DNA molecule develops a close up door structurewithout totally free ends. Just as is the case for linear DNA, elevated temperatures oralkaline pH ruin the hydrogen bonds and also other interactions the stabilizedouble-helical one DNA molecules. Unlike direct DNA, however, the twostrands of circular DNA cannot unwind and separate; attempts come melt such DNAresult in one interlocked, tangled massive of single-stranded DNA (Figure 4-10a).


Figure 4-10

Denaturation of circular DNA. (a) If both strands are closed circles, denaturation disrupts thedouble helix, however the two single strands end up being tangled around eachother and cannot separate. (b) If one or both strands are nicked,however, the 2 strands (more...)


Only if a aboriginal circular DNA is nicked (i.e., among thestrands is cut), will certainly the 2 strands unwind and separate as soon as the molecule isdenatured. In this case, one of the separated strands is circular, and the otheris direct (Figure 4-10b). Nicking ofcircular DNA wake up naturally throughout DNA replication and can be inducedexperimentally v a short concentration that deoxyribonuclease (a DNA-degradingenzyme), for this reason that just a single phosphodiester link in the molecule is cleaved.The examine of circular DNA molecules lacking free ends first uncovered thecomplicated geometric shape alters that the double-stranded DNA molecule mustundergo once the strands space not totally free to separate.


Local Unwinding of DNA induces Supercoiling

So much we have described DNA as a long constant helical structure that can havelocal perturbations, especially because of protein binding. In addition, as soon as thetwo end of a DNA molecule are fixed, the molecule exhibits a superstructureunder specific conditions. This occurs as soon as the base pairing is interrupted and alocal region unwinds. The anxiety induced through unwinding is relieved through twisting ofthe double helix top top itself, forming supercoils (Figure 4-11). Unwinding and subsequentsupercoiling occurs throughout replication, transcription, and also binding that manyproteins to circular DNAs or to long DNA loops whose ends are resolved withineukaryotic chromosomes. Supercoiling is recognized and also regulated by enzymescalled topoisomerases. Together discussedin later on chapters, these enzymes have critical role in both DNA replicationand the transcription of DNA into RNA.


Figure 4-11

Supercoiling in electron micrographs of DNA isolated indigenous theSV40 virus. As soon as isolated SV40 DNA is separated from its linked protein, theDNA duplex is underwound and also assumes the supercoiled configuration(form I). If one strand is nicked, the strands (more...)


RNA molecules Exhibit differed Conformations and also Functions

As detailed earlier, the primary structure that RNA is generally similar to the ofDNA; however, the street component (ribose) that RNA has secondary hydroxylgroup at the 2′ place (see Figure4-1b), and thymine in DNA is replaced by uracil in RNA (see number 4-2). The hydroxyl group onC2 the ribose makes RNA more chemically labile than DNA andprovides a chemically reactive team that takes part in RNA-mediated enzymaticevents. As a result of this lability, RNA is cleaved into mononucleotides byalkaline solution, whereas DNA is not. Like DNA, RNA is a lengthy polynucleotidethat have the right to be double-stranded or single-stranded, direct or circular. It have the right to alsoparticipate in a hybrid helix composed of one RNA strand and one DNA strand;this hybrid has a slightly various conformation 보다 the typical B form ofDNA.

Unlike DNA, i m sorry exists mostly in a single, really long three-dimensionalstructure, the dual helix, the various types of RNA exhibition differentconformations. Distinctions in the sizes and conformations that the miscellaneous typesof RNA permit them to carry out specific functions in a cell. The simplestsecondary structures in single-stranded RNAs are created by pairing ofcomplementary bases. “Hairpins” are developed by pairing ofbases in ~ ≈5 – 10 nucleotides of eachother, and also “stem-loops” by pairing the bases the areseparated by ≈50 to several hundred nucleotides (Figure 4-12a). These an easy folds cancooperate to type more complex tertiary structures, among which is termed a“pseudoknot” (Figure4-12b).


Figure 4-12

RNA an additional and tertiary structures. (a) Stem-loops, hairpins, and other secondary structures can type bybase pairing between distant complementary segment of an RNAmolecule. In stem-loops, the single-stranded loop (dark red) betweenthe base-paired (more...)


As disputed in detail later, tRNA molecules take on a well-definedthree-dimensional style in systems that is an important in protein synthesis.Larger rRNA molecules additionally have in your ar well identified three-dimensionalstructures, with an ext flexible web links in between. Second and tertiarystructures additionally have been recognized in mRNA, specifically near the end ofmolecules. These recently found structures are under energetic study. Clearly,then, RNA molecules are favor proteins in the they have structured domainsconnected by less structured, flexible stretches.

The folded domains of RNA molecule not only are structurally analogous to theα helices and β strands discovered in proteins, but in some casesalso have actually catalytic capacities. Such catalytic RNAs, called ribozymes, can reduced RNA chains. SomeRNA domains additionally can catalyze RNA splicing, a remarkableprocess in i m sorry an inner RNA sequence, an intron, is cut and removed and also the two resulting chains,the exons, are sealed together.This procedure occurs throughout formation the the majority of functional mRNAmolecules in eukaryotic cells, and also occurs in bacteria and archaea.Remarkably, some RNAs bring out self-splicing, with thecatalytic activity residing in the intron sequence. The mechanisms of splicingand self-splicing are disputed in information in thing 11. As provided later in this chapter, rRNA isthought to play a catalytic role in the development of peptide bond duringprotein synthesis.

In this chapter, we focus on the functions of mRNA, tRNA, and also rRNA in geneexpression — the procedure of getting theinformation in DNA converted right into proteins. In later chapters we will encounterother RNAs, often associated with proteins, that participate in other cellfunctions.

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