DNA: The Chemical Basis of Heredity

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DNA The Chemical Basis of Heredity
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• Chapter Goals
• History of how DNAs structure and function were
  discovered
• DNA replication
• Role of DNA in directing RNA synthesis
  (transcription)
• Role of DNA in directing protein synthesis
  (translation)

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The Transforming Principle Frederick Griffith
(1920s) (Serendipity is important in science!)
By 1920s Chromosomes made up of proteins and
DNA Butmost scientists did not think DNA was the
hereditary material.
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• From Griffiths work
• Some substance causes a heritable change between
  the S and R cells.
• What is it?

• Avery MacLeod, 1944
• Sequentially destroyed in S bacteria
• Proteins
• Lipids
• Carbohydrates
• DNA
• Then asked Which component of S bacteria, when
  NOT destroyed, was able to transform the R
  bacteria to become virulent?

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• Very important experimentbut not well received
  and generally disregarded by the scientific
  community.
• DNA is not complex enough to be the material of
  heredity.
• Bacteria are so simple, it is unlikely that they
  have DNA.

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1952 Hershey and Chase Used T2 bacteriophages
to show that DNA was the genetic material in
viruses
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• Making use of viruses The T2 bacteriophage
• Viruses, in general
• Are parasites! Not considered to be living
  organisms
• Insert their genetic material into host cell (Ex.
  bacteria, mucosa, T helper cells)
• Hijack host cell nutrients to make more virus
  particles
• May or not lyse (blow up) the host cell
• Fairly simplecontain a shell of protein and a
  strand of DNA inside

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Lytic
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Hershey Chase (1952) Which part of the virus
enters the bacteria? The DNA or the PROTEIN?
Phosphorus is found in DNANOT in proteins Use
32P to label DNA
Sulfur is found in proteinsnot in DNA Use 35S
to label protein
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DNA is indeed the hereditary material in things
as simple as viruses! (Just 60 years ago!)
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The Structure of DNA
X-Ray Crystallography (Rosalind Franklin) DNA
is helical
Chargoffs Rule Amount of A Amount of
T Amount of C Amount of G Quantity of
Pyrimidines Quantity of Purines
Previous Modeling Experiments DNA is likely
made up of 2 chains These 2 chains run
antiparallel
This is the information that Watson Crick
started with
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Watson Cricks Model
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Anatomy of a Nucleotide
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C
P P P-O-
Nitrogenous Base (A, C, T, G)
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C
C
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Pentose Sugar
C
C
3
2
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Nucleotide is made of Nitrogenous base
(A,C,G,T) Deoxyribose Sugar Phosphate
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3
5
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How Does DNA Replicate? 3 possibilities
Semiconservative Replication Each new molecule
has 1 old strand and 1 new strand.
YES!
NO!
NO!
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Meselson-Stahl Experiment (Proof that DNA
Replication is Semiconservative)
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Rules of DNA Replication

• All chromosomes have at least one origin of
  replication (ori)
• Prokaryotes have only 1.
• Eukaryotic chromosomes have many.
• A huge protein complex, call the REPLICATION
  COMPLEX, binds to the ori
• 3. Each new DNA strand grows ONLY IN THE
• 5 to 3 DIRECTION

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What does 5 to 3 mean?
C 5
C 3
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• Steps Involved in DNA Replication
• Helicase unwinds the double helix (Helicase
  hacks!)
• Primase lays down an RNA primer (Primase primes!)
• DNA polymerase pastes in nucleotides (Polymerase
  pastes!)
• Ligase joins the smaller Okazaki fragments and
  rips up the RNA primer (Ligase links!)

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What Happens at the End of the Line?
Part of the end of each chromosome is lost
following each round of replication (anywhere
from 50-200 base pairs).
Telomeres The end portions of a chromosome made
up of a repeating sequence of DNAdoes NOT
contain a gene.
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Telomerase An Enzyme to the Rescue
But...Is telomerase always a good thing?
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What happens when there is a mistake?

• DNA polymerase 1,000 base pairs per second
• 11,000,000 error rate (1,000 errors every time
  DNA is replicated

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Only 1 error in 1010 bases remains