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6.4 DNA Replication   195


                        3.  Summarize the key factors DNA polymerase requires to   Figure 6.18  The model of DNA replication postulated by
                            replicate DNA.                                 Watson and Crick. Unwinding of the double helix allows each of
                        4.  Outline the steps in the process of DNA replication and   the two parental strands to serve as a template for the synthesis of
                            how they relate to the requirements of DNA     a new strand by complementary base pairing. The end result: A
                            polymerase.                                    single double helix is transformed into two identical daughter
                                                                           double helixes.
                        5.  Discuss three ways cells preserve the accuracy and
                            integrity of the genetic information in DNA.
                                                                                                             A T
                                                                                                          T  A
                                                                                                       G   C
                       In one of the most famous understatements in the scien-                        CG
                       tific literature, Watson and Crick wrote at the end of   1. Original double helix
                       their 1953 paper proposing the double helix model: “It                         A  T
                       has not escaped our notice that the specific pairing we                        A    T
                       have postulated immediately suggests a possible copying                          T  G  A C
                       mechanism for the genetic material.” This copying, as                              C     G
                       we saw in Chapter 4, must precede the transmission of                  Template  T           A  Template
                       chromosomes from one generation to the next via meio-  2. Strands separate.  T                   A
                       sis, and it is also the basis of the chromosome duplica-                    A  T             A  T
                       tion prior to each mitosis that allows two daughter cells   3. Complementary  T  A        T      A
                                                                             bases align opposite
                       to receive a complete copy of the genetic information in     templates.  C    G           C     G
                       a progenitor cell.                                                      G  C              G  C
                                                                                               G  C               G  C
                                                                                               T    A             T   A
                       Overview: Complementary Base                        4. Enzymes link       T   A             T    A
                                                                             sugar-phosphate
                       Pairing Ensures Semiconservative                      backbone of aligned   CG    Daughter    CG
                       Replication                                           nucleotides into a      G  C  helixes     G  C
                                                                             continuous new strand.
                                                                                                  G   C             G   C
                       In the process of replication postulated by Watson and Crick,           C   G             C   G
                       the double helix unwinds to expose the bases in each strand            A T               A T
                       of DNA. Each of the two separated strands then acts as a
                       template, or molecular mold, for the synthesis of a new sec-
                       ond strand (Fig. 6.18). The newly replicated strands form as                    Templates
                       complementary bases align opposite the exposed bases on                         New strands
                       the two parental strands. That is, an A at one position on the
                       original strand signals the addition of a T at the correspond-
                       ing position on the newly forming strand; a T on the original
                       signifies the addition of an A; similarly, G calls for C, and C
                       calls for G, as demanded by complementary base pairing.  two possible alternatives. With conservative replication,
                          Once the appropriate base has aligned opposite to and   one of the two daughter  double helixes would consist
                       formed hydrogen bonds with its complement, enzymes join   entirely of original DNA strands, while the other helix
                       the base’s nucleotide to the preceding nucleotide by a phos-  would consist of two newly synthesized strands. With
                       phodiester bond, eventually linking a whole new line of   dispersive  replication, both daughter double helixes
                       nucleotides into a continuous strand. This mechanism of   would carry blocks of original DNA interspersed with
                       DNA strand separation and complementary base pairing   blocks of newly synthesized material. These alternatives
                       followed by the coupling of successive nucleotides yields   are less satisfactory because they do not immediately
                       two daughter double helixes that each contain one of the   suggest a mechanism for copying the information in the
                       original DNA strands intact (this strand is conserved) and   sequence of bases.
                       one completely new strand (Fig. 6.19a). For this reason,
                       such a pattern of double helix duplication is called semi-
                       conservative replication: a copying in which one strand of   Experiments with Heavy Nitrogen Verify
                       each new double helix is conserved from the parent mole-  Semiconservative Replication
                       cule and the other is newly synthesized.
                          Watson and Crick’s proposal is not the only replica-  In 1958, Matthew Meselson and Franklin Stahl performed
                       tion mechanism imaginable. Figures 6.19b and c illustrate   an experiment that confirmed the semiconservative nature
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