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CHAPTER 11 DNA and Its Role in Heredity

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CHAPTER 11 DNA and Its Role in Heredity. The Structure of DNA. In the 1950 ’ s many researchers were trying to determine the structure of DNA. X-ray crystallography showed that the DNA molecule is a helix. (Franklin & Wilkins)

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the structure of dna
The Structure of DNA
  • In the 1950’s 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?
the structure of dna4
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?
structure of dna
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
structure of dna6
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.
dna structure
DNA Structure
  • Examine the other side of the DNA molecule.
  • It just the opposite
the structure of dna11
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).
three models for dna replication
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
the structure of dna13
The Structure of DNA
  • The sugar–phosphate 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).
dna replication
DNA Replication
  • Meselson and Stahl’s 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.
two steps of dna replication
Two Steps of DNA Replication
  • The DNA is denatured.
  • New nucleotides are covalently bonded to the each growing strand.
the mechanism of dna replication
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 substrate’s phosphate groups, deoxyribonucleoside triphosphates, a bond breaks releasing two of the phosphate groups, releasing energy for DNA synthesis
  • Review Figure 11.11
the mechanism of dna replication20
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
the mechanism of dna replication22
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.
many proteins assist in dna replication
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.
the mechanism of dna replication26
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
summary of dna replication
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.
summary of dna replication29
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.
summary of dna replication30
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.
dna proofreading and repair
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
proofreading mechanism
Proofreading Mechanism
  • DNA polymerase recognizes a typo, an extra base, deletes it and adds the correct base.
  • Synthesis continues
mismatch repair mechanism
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.
excision repair mechanism
Excision Repair Mechanism
  • Removes abnormal bases due to chemical damages and replaces them with functional bases. (Example, skin cancer)
  • Enzymes inspect the cell’s 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.