CHAPTER 11 DNA and Its Role in Heredity

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CHAPTER 11DNA and Its Role in Heredity
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The Structure of DNA

• In the 1950s many researchers were trying to
  determine the structure of DNA.
• X-ray crystallography showed that the DNA
  molecule is a helix. (Franklin Wilkins)
• Chargaff discovered that the amount of adenine
  equals the amount of thymine and the amount of
  guanine equals the amount of cytosine.
• What does this finding indicate?

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Figure 11.5
figure 11-05.jpg
Figure 11.5
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The Structure of DNA

• Watson and Crick proposed that DNA is a
  double-stranded helix with the two sides of DNA
  running in opposite directions (the strands are
  antiparallel),
• The two sides are held together by hydrogen
  bonds.
• What accounts for the uniform diameter of the
  double helix?

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Structure of DNA

• A purine (A or G) consists of a double ring
  molecule. A pyrimidine (C or T) consists of a
  single ring molecule. A purine always bonds with
  a pyrimidine thus maintaining a constant distance
  between the two sides of the DNA molecule.
• Review Figures 11.6 and 11.7

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Structure of DNA

• What does it mean - the two DNA strands run in
  opposite directions?
• Examine the phosphodiester bonds between
  nucleotides.
• The 3 carbon of one deoxyribose and the 5
  carbon of another deoxyribose are bonded.
• One side of the DNA molecule has an unconnected
  5 phosphate group while the opposite end has an
  unconnected 3 hydroxyl group.

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DNA Structure

• Examine the other side of the DNA molecule.
• It just the opposite

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Figure 11.6
figure 11-06.jpg
Figure 11.6
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Figure 11.7 Part 1
figure 11-07a.jpg
Figure 11.7 - Part 1
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Figure 11.7 Part 2
figure 11-07b.jpg
Figure 11.7 Part 2
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The Structure of DNA

• Three features summarize the molecular
  architecture of DNA
• The DNA molecule is a double-stranded helix.
• The diameter of the DNA molecule is uniform.
• The two strands run in different directions (they
  are antiparallel).

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Three Models for DNA Replication

• Conservative original plus new strand
• Dispersive fragments of original DNA serve as
  templates for two DNA molecules.
• Semiconservative parent strand serves as a
  template for new strand
• Review Figure 11.8

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The Structure of DNA

• The sugarphosphate backbones of each strand coil
  around the outside of the helix.
• The nitrogenous bases point toward the center of
  the helix.
• Hydrogen bonds between complementary bases hold
  the two strands together.
• A always pairs with T (two hydrogen bonds).
• G always pairs with C (three hydrogen bonds).

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Figure 11.7 Base Pairing in DNA Is Complementary
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Figure 11.8
figure 11-08.jpg
Figure 11.8
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DNA Replication

• Meselson and Stahls experiment (1957) proved
  replication of DNA to be semiconservative
• A parent strand is a template for synthesis of a
  new strand
• Two replicated DNA helices contain one parent
  strand and one synthesized strand each.

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Two Steps of DNA Replication

• The DNA is denatured.
• New nucleotides are covalently bonded to the each
  growing strand.

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The Mechanism of DNA Replication

• Nucleotides are always added to the growing 3
  end. Nucleotides are added by complementary base
  pairing with the template strand
• The free hydroxyl group reacts with one of the
  substrates phosphate groups, deoxyribonucleoside
  triphosphates, a bond breaks releasing two of
  the phosphate groups, releasing energy for DNA
  synthesis
• Review Figure 11.11

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Figure 11.11
figure 11-11.jpg
Figure 11.11
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The Mechanism of DNA Replication

• No DNA forms without a primer.
• A primer is a short segment of DNA or RNA that
  starts replication.
• An enzyme, RNA primase, catalyzes the synthesis
  of short RNA primers
• Review Figure 11.15

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Figure 11.15
figure 11-15.jpg
Figure 11.15
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The Mechanism of DNA Replication

• DNA polymerase action causes the emerging
  leading strand to grow in the 5-to-3 direction.
  
• RNA primer is degraded and DNA replaces it.

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Many Proteins Assist in DNA Replication

• DNA helicases unwind the double helix,
• Binding proteins keep the two strands separated.
• RNA primases makes the primer strand.
• DNA polymerase adds nucleotides, proofreads DNA
  and repairs it.
• DNA ligase seals up breaks in the sugar-phosphate
  backbone.

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Figure 11.16
figure 11-16.jpg
Figure 11.16
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Figure 11.17
figure 11-17.jpg
Figure 11.17
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The Mechanism of DNA Replication

• On the lagging strand, growing away from the
  replication fork, DNA is made in the 5-to-3
  direction but synthesis is discontinuous DNA is
  added as short fragments to primers, then the
  polymerase skips past the 5 end to make the next
  fragment.
• Review Figures 11.16, 11.17 and 11.18

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Figure 11.18
figure 11-18.jpg
Figure 11.18
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Summary of DNA Replication

• The replication begins at origins of replication
  - specific sequence of nucleotides which
  recognizes helicase.
• Helicase unwinds the parental DNA.
• Single-strand binding proteins stabilize the
  unwound parental DNA.
• Replication of DNA then proceeds in both
  directions.

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Summary of DNA Replication

• Primase joins RNA nucleotides to make a primer (
  10 nucleotides long) to begin synthesis of the
  leading strand.
• As nucleotides align with complementary bases
  along a template strand of DNA, they are added by
  polymerase, to the growing end of the new strand
  (50/second in human cells).
• DNA polymerases add nucleotides only to the free
  3 end of the growing DNA strand.

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Summary of DNA Replication

• The leading strand is synthesized continuously in
  the 5 to 3 direction by DNA polymerase.
• The lagging strand is synthesized discontinously.
  Primase synthesizes short RNA primers to form
  Okazaki fragments.
• The RNA primers are later replaced with DNA.
• DNA ligase joins the Okazaki fragment to the
  growing strand.

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DNA Proofreading and Repair

• There is about about one error in 106 nucleotides
  bases added in DNA replication. That means about
  1000 genes in every cell would be affected each
  time the cell divided.
• Errors are repaired by proofreading, mismatch
  repair, and excision repair.
• Review Figure 11.19

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Proofreading Mechanism

• DNA polymerase recognizes a typo, an extra base,
  deletes it and adds the correct base.
• Synthesis continues

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Mismatch Repair Mechanism

• The repair mechanism detects the wrong base
  before methylation has occurred.
• Methyl groups (-CH3) are added to some cytosines.
• Unmethylated strands are targeted for
  inspections.
• A form of colon cancer arises from failure of
  mismatch repair.

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Excision Repair Mechanism

• Removes abnormal bases due to chemical damages
  and replaces them with functional bases.
  (Example, skin cancer)
• Enzymes inspect the cells DNA and cut the
  defective strand.
• Another enzyme cuts away adjacent bases and the
  offending bases.
• DNA polymerase synthesizes a new correct piece to
  replace the discarded one.
• DNA ligase seals the new base in place.

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Figure 11.19
figure 11-19.jpg
Figure 11.19