Chapter 16 The Molecular Basis of Inheritance

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Chapter 16 The Molecular Basis of Inheritance
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OBJECTIVES

• DNA as the Genetic Material
• Explain why researchers originally thought
  protein was the genetic material.
• Summarize the experiments performed by the
  following scientists that provided evidence that
  DNA is the genetic material
• Frederick Griffith
• Oswald Avery, Maclyn McCarty, and Colin MacLeod
• Alfred Hershey and Martha Chase
• Erwin Chargaff
• Explain how Watson and Crick deduced the
  structure of DNA and describe the evidence they
  used. Explain the significance of the research of
  Rosalind Franklin.
• Describe the structure of DNA. Explain the
  base-pairing rule and describe its
  significance.   

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Background

• DNA and Transforming Bacteria
• F. Griffiths and streptococcus pneumoniae
• R (rough coat) cells acquired from dead S (smooth
  coat) cells had the ability to make
  polysaccharide coats
• This phenomenon is now called transformation

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Griffiths worked with two strains of the
bacteriumA pathogenic strain (S strain causes
pneumonia) and a nonpathogenic strain (R strain)
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Griffith called the phenomenon transformation

• Defined as a change in genotype and phenotype due
  to the assimilation of external DNA by a cell
• The R strain cells provided heat killed S strain
  cells with a vessel for genetic material

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Transformation and Avery

• Avery isolated DNA as the transforming agent
• Purified various parts of heat-killed pathogenic
  bacteria attempted transformation with each
  into a nonpathogenic bacteria
• Found that only DNA transformed the nonpathogenic
  bacteria to pathogenic

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Bacteriophage Virus that attacks or infects
bacteria, uses host machinery to reproduce
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Viruses Can Program Cells

• Hershey and M. Chase experiments
• Worked with T2 phages and E. coli
• Tagged proteins and DNA
• Concluded
• Viral proteins remain outside the host cell
• Viral DNA is injected into host cell
• Injected DNA molecules produces more viruses
• Nucleic acids are hereditary material

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Additional Evidence DNA is Genetic Material of
Cells

• Eukaryotic cell doubles DNA prior to mitosis
• During mitosis, DNA is equally divided
• Diploid cells have 2x DNA as haploid cells
• Erwin Chargaff and his rules
• AT, CG

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Chargaffs Rules

• Erwin Chargaff analyzed the base composition of
  DNA from a number of different organisms
• In 1947, he reported that DNA composition varies
  from one species to the next
• Regularity in the ratios of nucleotide bases
• For every A, is a T
• For every G, is a C
• This evidence of molecular diversity among
  species made DNA a more credible candidate for
  the genetic material

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The Double Helix

• History
• Linus Pauling proposed a 3-stranded model of DNA
• Rosalind Franklin An x-ray photographer who
  took the photo that enabled Watson and Crick to
  deduce the double helical structure of DNA

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• Franklin had concluded
• DNA was composed of two antiparallel
  sugar-phosphate backbones, with the nitrogenous
  bases paired in the molecules interior
• The nitrogenous bases
• Are paired in specific combinations adenine with
  thymine, and cytosine with guanine

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• James Watson and Francis crick deduced the
  structure of DNA based on x-ray diffraction photo
  of DNA

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• There is additional specificity of pairing
• Dictated by the structure of the bases
• If a purine binds with a purine structure too
  wide compared to the measured width of DNA
• If pyrimidine binds with pyrimidine structure
  too narrow
• Purine pyrimidine width consistent with X-ray
  measurement
• Each base pair forms a different number of
  hydrogen bonds
• Adenine and thymine form two bonds, cytosine and
  guanine form three bonds

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Chapter 15 DNA Replication
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• DNA Replication and Repair
• Describe the semiconservative model of
  replication and the experiments of Matthew
  Meselson and Franklin Stahl.
• Describe the process of DNA replication,
  including the role of the origins of replication
  and replication forks.
• Explain the role of DNA polymerases in
  replication.
• Explain what energy source drives the
  polymerization of DNA.
• Define antiparallel and explain why continuous
  synthesis of both DNA strands is not possible.
• Distinguish between the leading strand and the
  lagging strand.
• Describe the significance of Okazaki fragments.
• Explain the roles of DNA ligase, primer, primase,
  helicase, topoisomerase, and single-strand
  binding proteins.
• Explain the roles of DNA polymerase, mismatch
  repair enzymes, and nuclease in DNA proofreading
  and repair.
• Describe the structure and function of telomeres.
• Explain the possible significance of telomerase
  in germ cells and cancerous cells.

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DNA Replication
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• Semi-conservative Replication

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B. Meselson-Stahl Experiment
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Steps of Replication

• Strand Separation
• Helicases catalyze unwinding
• Single stranded binding proteins stabilize the
  unwound DNA

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• Synthesis of DNA Strands
• New nucleotides align along old strand
• DNA polymerase links nucleotides in a 5? 3
  direction
• Hydrolysis of nucleoside triphosphates provide
  energy

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• DNA Strands Antiparallel
• Leading strand continuous synthesis of DNA
  toward replication fork

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• Lagging strand discontinuous synthesis of DNA
  away from replication
• Okazaki fragments
• DNA ligase links Okazaki fragments

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• Priming DNA Synthesis
• Primers short segments of RNA
• Primer formation precedes DNA replication,
  because DNA polymerase can only add bases to an
  existing polynucleotide
• DNA polymerase removes RNA primer and replaces it
  with DNA