The Molecular Basis of Inheritance

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The Molecular Basis of Inheritance

• Chapter 16

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Figure 16.2 Transformation of bacteria
1928 Fred Griffith- Streptococcus pneumoniae
S- smooth (pathogenic) with capsule R-rough
(non-pathogenic) without capsule
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Oswald Avery and Colin MacLeod (1944)

• Built upon Griffiths experiment
• Separated components of bacteria
• activity moved with DNA
• Only DNA transformed non-pathogenic cells
• lipids and proteins did not
• DNase destroyed transformation activity
• proteases and RNAses did not
• Therefore?

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Figure 16.3 The Hershey-Chase experiment phages
Alfred Hershey and Martha Chase, 1952
Use of radioactive isotopes

• 32P Phosphorous present in nucleic acids but not
  much in proteins (normal30P)
• 35S Sulphur (sulfur?) present in proteins but
  not in nucleic acids (normal 32S)
• Can use these isotopes as tracers to follow DNA
  and proteins

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Figure 16.4 Alfred Hershey and Martha Chase 1952
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Components of DNA Deoxyribonucleic acid
Phosphodiester bond
Hydrogen bonds
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Chargaffs rule

• the amount of adenine present always equals the
  amount of thymine, and the amount of guanine
  always equals the amount of cytosine. Erwin
  Chargaff
• A T
• C G

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Figure 16.7 The double helix
Major groove and minor groove
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Purine and pyrimidine
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Anti parallel strands
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Figure 16.9 A model for DNA replication the
basic concept (Layer 1)
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Figure 16.9 A model for DNA replication the
basic concept (Layer 2)
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Figure 16.9 A model for DNA replication the
basic concept (Layer 3)
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Figure 16.9 A model for DNA replication the
basic concept (Layer 4)
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Figure 16.10 Three alternative models of DNA
replication
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Figure 16.11 The Meselson-Stahl experiment
tested three models of DNA replication
Density centrifugation
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Figure 16.11 The Meselson-Stahl experiment
tested three models of DNA replication
Density centrifugation
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DNA replication

• Double helix contains basis for its own
  replication
• Semi conservative
• 5 to 3 direction
• 1000 bases per second

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Figure 16.12 Origins of replication in eukaryotes
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Re-replication block

• DNA contains Origin Recognition Complex (ORC)
  binding sites that allow initiation of DNA
  replication
• These sites are blocked (by phosphorylation of
  ORC by S-Cdk) once replication begins
• They cannot be unblocked until after mitosis is
  complete (after M-Cdk innactivation)

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DNA replication

• Synthesis occurs in a 5 to 3 direction
• DNA strands in an antiparallel arrangement
• Two strands therefore synthesized in opposite
  direction

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DNA polymerase III complex

• 10 proteins per subunit
• Two complexes act as dimer to synthesize both
  strands simultaneously
• ?-subunit
• catalytic
• 1000 bases/second
• ?-subunit
• proofreading
• ?2-subunit (Sliding clamp)
• clamps enzyme to DNA

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DNA polymerase III complex (part deux)

• Requires a short stretch of double-stranded
  material as a primer.
• DNA-RNA hybrid synthesized by primase

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Figure 16.14 Synthesis of leading and lagging
strands during DNA replication

• Synthesis occurs in a 5 to 3 direction (new
  strand)
• DNA strands in an antiparallel arrangement
• Two strands therefore synthesized in opposite
  direction

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Figure 16.15 Priming DNA synthesis with RNA

• DNA polymerase III
• Synthesizes DNA
• DNA polymerase I
• Erases primer,fills gaps with DNA
• DNA ligase
• Joins the gaps

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Figure 16.16 A summary of DNA replication
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Simultaneous synthesis required twist in lagging
strand
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Figure 16.17 Nucleotide excision repair of DNA
damage
Xeroderma pigmentosum
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Figure 16.18 The end-replication problem
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Figure 16.18 Telomeres and telomerase
Figure 16.19 Telomeres and telomerase Telomeres
of mouse chromosomes Human telomere TTAGGG
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