Molecular Biology

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Molecular Biology

• Part II The Central Dogma
• The Hereditary Molecule
• Replication Repair

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From MM to Results

• Previously we focused on Materials and Methods
  per se
• Now course focus changes to inferences from
  experiments
• structures and functions of hereditary molecules
• empirical tests and interpretations

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Griffiths (1928) experiment with Streptococcus
( Diplococcus) pneumoniae
Living, Virulent Cells
Living, Non-Virulent Cells
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Avery, McLeod, McCarty (1944) isolation of
the transforming principle
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Oswald Avery, from Judson HF The Eighth Day of
Creation
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Data from Avery, McLeod, McCarty
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Data from Avery, McLeod, McCarty
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The Transforming Principle alternative
interpretations (Lederberg 1994, 1956)

• A specific mutagen with a special ability to
  direct a particular gene to mutate in a specific
  direction
• A polysaccharide autocatalyst (perhaps complexed
  with DNA) that primes an enzymatic reaction for
  polysaccharide synthesis

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The Transforming Principle alternative
interpretations (Lederberg 1994, 1956)

• A specific mutagen with a special ability to
  direct a particular gene to mutate in a specific
  direction
• A polysaccharide autocatalyst (perhaps complexed
  with DNA) that primes an enzymatic reaction for
  polysaccharide synthesis

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The Transforming Principle alternative
interpretations (Lederberg 1994, 1956)

• A bacterial virus, which on infecting the
  bacteria provoked capsule synthesis as a host
  reaction
• Something that acted at a distance, without
  penetrating the bacteria
• An element sui generis for which no general
  concept should be adduced

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The Transforming Principle alternative
interpretations (Lederberg 1994, 1956)

• A bacterial virus, which on infecting the
  bacteria provoked capsule synthesis as a host
  reaction
• Something that acted at a distance, without
  penetrating the bacteria
• An element sui generis for which no general
  concept should be adduced

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The Transforming Principle alternative
interpretations (Lederberg 1994, 1956)

• A bacterial virus, which on infecting the
  bacteria provoked capsule synthesis as a host
  reaction
• Something that acted at a distance, without
  penetrating the bacteria
• An element sui generis for which no general
  concept should be adduced

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Hershey Chase (1952) the blender experiment
Weaver 2005 Molecular Biology
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Martha Chase and Alfred Hershey
Judson, H.F. The Eighth Day of Creation
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Chargaffs data
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Arms Camp Biology
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Judson, HF. The Eighth Day of Creation
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Number 51
Franklins X-ray diffraction of DNA, from Judson,
HF. The Eighth Day of Creation
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Arms Camp Biology
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Tautomers matter standard expectation was that
adenine occurred in imino form thymine in the
enol form or that both forms occurred in rapid
exchange
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ANTI- parallel
Arms Camp Biology
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Judson HF The Eighth Day Of Creation
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Maurice Wilkins
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John Kendrew
Max Perutz
hemoglobin
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Z
B
A
No. 51 is a diffraction image of B form DNA
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Arms Camp Biology
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Radman Wagner Sci. Amer. 1988
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relaxed plasmid
supercoiled
more supercoiled
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Meselson Stahls demon- stration of
semi- conservative replication
Arms Camp Biology
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Holmes, FL. 2001 From Comfort, N. 2001 Science
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Weaver 2005 Molecular Biology
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Watson et al. 1987 Molecular Biology of the Gene
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Watson et al. 1987 Molecular Biology of the Gene
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Watson et al. 1987 Molec. Biol. of the Gene
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Weaver 2005 Mol. Biol.
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Gary Larson The Far Side
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Nucleotide selection
Radman Wagner 1988 Sci. Amer.
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Radman Wagner 1988 Sci. Amer.
Proofreading
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Mismatch repair
Radman Wagner 1988 Sci. Amer.
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Radman Wagner 1988 Sci. Amer.
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Radman Wagner 1988 Sci. Amer.
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Freifelder D. Molecular Biology
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Freifelder D. Molecular Biology
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Alkylation damage e.g. methylation of O6 on
guanine interferes with normal H-bonding can be
repaired by O6-guanine-methyltransferase
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O6-guanine-methyltransferase a suicide
enzyme also called ADA Alkylation Damage
repair
ADA also stands for an entirely different
enzyme in humans
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Human DNA repair genes entire table is 2 1/3
pages long!
AP endonuclease
O6 meG alkyl transferase
mismatch repair group
Wood et al. 2001 Science
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Why would one want to inhibit repair of
DNA damage?
AGT O6-Me-G Transferase in mammals
Genetic Engineering News
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Weaver 2005 Mol. Biol.