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This fidelity ismuch higherthan one would expectfrom the accuracyof complementarybaseFigure5-5 The semiconservativenature of DNA replication.In a round ofreplication,eachof the two strandsof DNA is usedas a templatefor theformationof a complementaryDNAstrand.Theoriginalstrandsthereforeremainintactthroughmanycellgenerations.,a\/REPLTCATTON\,r\..REPLICATION269DNA REPLICATIONMECHANISMSFigure5-6Two replicationforks movingin oppositedirectionson a circularchromosome.An activezoneof DNAalongamovesprogressivelyreplicationcreatingaDNAmolecule,replicatingDNAstructureknownasaY-shaoedfork:the two armsof eachYreplicationarethe two daughterDNAmolecules,and the stemof the Y is the parentalDNAhelix.In this diagram,parentalstrandsareorange;newly synthesizedstrandsarecourtesyof Jeromered.(MicrographVinograd.)-/replicationforks-1umpairing.
The standard complementary base pairs (see Figure 4-4) are not theonly ones possible. For example, with small changes in helix geometry, twohydrogen bonds can form between G and T in DNA. In addition, rare tautomericforms of the four DNA bases occur transiently in ratios of I part to lOa or 105.These forms mispair without a change in helix geometry: the rare tautomericform of C pairs with A instead of G, for example.If the DNA polymerase did nothing special when a mispairing occurredbetween an incoming deoxyribonucleosidetriphosphate and the DNA template,the wrong nucleotide would often be incorporated into the new DNA chain, producing frequent mutations. The high fidelity of DNA replication, however,depends not only on the initial base-pairing but also on several "proofreading"mechanisms that act sequentially to correct any initial mispairings that mighthave occurred.DNA polymerase performs the first proofreading step just before a newnucleotide is added to the growing chain.
Our knowledge of this mechanismcomes from studies of several different DNA polymerases, including one produced by a bacterial virus, T7, that replicates inside E. coli. The correctnucleotide has a higher affinity for the moving polymerase than does the incorrect nucleotide, because the correct pairing is more energetically favorable.Moreover, after nucleotide binding, but before the nucleotide is covalentlyadded to the growing chain, the enzyme must undergo a conformational changein which its "fingers" tighten around the active site (seeFigure 5-4). Becausethischange occurs more readily with correct than incorrect base-pairing, it allowsthe polymerase to "double-check" the exact base-pair geometry before it catalyzesthe addition of the nucleotide.The next error-correcting reaction, knornrn as exonucleolytic proofreadingtakes place immediately after those rare instances in which an incorrectnucleotide is covalently added to the growing chain.
DNA polymerase enzymes+most recentlysYnthesizedDNAs',5Figure5-7 The structureof a DNAreplicationfork. Becauseboth daughterDNAstrandsare polymerizedin the 51toon the3'direction,the DNAsynthesizedlaggingstrandmust be madeinitiallyasacalledseriesof<b>Текст обрезан, так как является слишком большим</b>.
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