DNA: The Genetic Material

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DNA The Genetic Material

• Chapter 13

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The Genetic Material

• Frederick Griffith, 1928
• studied Streptococcus pneumoniae, a pathogenic
  bacterium causing pneumonia
• there are 2 strains of Streptococcus
• S strain is virulent
• R strain is nonvirulent
• Griffith infected mice with these strains hoping
  to understand the difference between the strains

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The Genetic Material

• Griffiths results
• live S strain cells killed the mice
• live R strain cells did not kill the mice
• heat-killed S strain cells did not kill the mice
• heat-killed S strain live R strain cells killed
  the mice

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The Genetic Material

• Griffiths conclusion
• information specifying virulence passed from the
  dead S strain cells into the live R strain cells
• Griffith called the transfer of this information
  transformation

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The Genetic Material

• Avery, MacLeod, McCarty, 1944
• repeated Griffiths experiment using purified
  cell extracts and discovered
• removal of all protein from the transforming
  material did not destroy its ability to transform
  R strain cells
• DNA-digesting enzymes destroyed all transforming
  ability
• the transforming material is DNA

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The Genetic Material

• Hershey Chase, 1952
• investigated bacteriophages viruses that infect
  bacteria
• the bacteriophage was composed of only DNA and
  protein
• they wanted to determine which of these molecules
  is the genetic material that is injected into the
  bacteria

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The Genetic Material

• Bacteriophage DNA was labeled with radioactive
  phosphorus (32P)
• Bacteriophage protein was labeled with
  radioactive sulfur (35S)
• radioactive molecules were tracked
• only the bacteriophage DNA (as indicated by the
  32P) entered the bacteria and was used to produce
  more bacteriophage
• conclusion DNA is the genetic material

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DNA Structure

• DNA is a nucleic acid.
• The building blocks of DNA are nucleotides, each
  composed of
• a 5-carbon sugar called deoxyribose
• a phosphate group (PO4)
• a nitrogenous base
• adenine, thymine, cytosine, guanine

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DNA Structure

• The nucleotide structure consists of
• the nitrogenous base attached to the 1 carbon of
  deoxyribose
• the phosphate group attached to the 5 carbon of
  deoxyribose
• a free hydroxyl group (-OH) at the 3 carbon of
  deoxyribose

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DNA Structure

• Nucleotides are connected to each other to form a
  long chain
• phosphodiester bond bond between adjacent
  nucleotides
• formed between the phosphate group of one
  nucleotide and the 3 OH of the next nucleotide
• The chain of nucleotides has a 5 to 3
  orientation.

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DNA Structure

• Determining the 3-dimmensional structure of DNA
  involved the work of a few scientists
• Erwin Chargaff determined that
• amount of adenine amount of thymine
• amount of cytosine amount of guanine
• This is known as Chargaffs Rules

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DNA Structure

• Rosalind Franklin and Maurice Wilkins
• Franklin performed X-ray diffraction studies to
  identify the 3-D structure
• discovered that DNA is helical
• discovered that the molecule has a diameter of
  2nm and makes a complete turn of the helix every
  3.4 nm

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DNA Structure

• James Watson and Francis Crick, 1953
• deduced the structure of DNA using evidence from
  Chargaff, Franklin, and others
• proposed a double helix structure

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DNA Structure

• The double helix consists of
• 2 sugar-phosphate backbones
• nitrogenous bases toward the interior of the
  molecule
• bases form hydrogen bonds with complementary
  bases on the opposite sugar-phosphate backbone

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DNA Structure

• The two strands of nucleotides are antiparallel
  to each other
• one is oriented 5 to 3, the other 3 to 5
• The two strands wrap around each other to create
  the helical shape of the molecule.

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DNA Replication

• Matthew Meselson Franklin Stahl, 1958
• investigated the process of DNA replication
• considered 3 possible mechanisms
• conservative model
• semiconservative model
• dispersive model

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DNA Replication

• Meselson and Stahl concluded that the mechanism
  of DNA replication is the semiconservative model.
• Each strand of DNA acts as a template for the
  synthesis of a new strand.

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DNA Replication

• DNA replication includes
• initiation replication begins at an origin of
  replication
• elongation new strands of DNA are synthesized
  by DNA polymerase
• termination replication is terminated
  differently in prokaryotes and eukaryotes

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DNA Repair

• DNA-damaging agents
• repair mechanisms
• specific vs. nonspecific mechanisms
• Mistakes during DNA replication can lead to
  changes in the DNA sequence and DNA damage.
• DNA can also be damaged by chemical or physical
  agents called mutagens.
• Repair mechanisms may be used to correct these
  problems.

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DNA Repair

• DNA repair mechanisms can be
• specific targeting a particular type of DNA
  damage
• photorepair of thymine dimers
• non-specific able to repair many different
  kinds of DNA damage
• excision repair to correct damaged or mismatched
  nitrogenous bases

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Timeline of Molecular history

• 1859 Charles Darwin no clue about genes
• 1865 Gregor Mendel lost until 1900
• 1869 Friedrich Mieshcer - DNA
• 1900 Hugo de Vries rediscovers Mendel
• 1902 Archibold Garrod genetic cause of a human
  disease
• 1902 Sutton and Boveri chromosome theory
• 1920 T.H. Morgan genes on chromosomes
• 1913 A.H. Sturtevant linkage map
• 1927 H.J. Muller x-ray induced mutations
• 1941 G. Beadle and E.L. Taum one gene one
  enzyme
• 1944 O.T. Avery, C. McLeod, Maclyn McCarty -
  proposed DNA genes
• 1950 E, Chargaff DNA base composition rules
• 1953 J.Watson, F. Crick, R.Franklin and M.Wilkins
  DNA structure

• 1958 M. Messelson and F. Stahl DNA replication
• 1961 S.Brenner, F.Jacob, M. Messelson mRNA
  discovered
• 1966 M. Niernberg, G.Khoroana Genetic code
• 1970 H. Smith restriction enzymes
• 1972 P. Berg first recombinant DNA
• 1973 H. Boyer, S.Cohen first cloned DNA
  fragment
• 1977 W.Gilbert, F.Sanger DNA sequencing first
  virus sequenced
• 1981- first transgenic mammals
• 1985 Alec Jeffreys DNA fingerprinting
• 1985 Kary Mullis PCR amplification
• 1990 J.Watson Human Gneome Project
• 1993 Huntiningtons Disease Group first
  identified genetic disease gene
• 1995 C.VentnerH.Smith base sequences of H.
  influenzae and M. genitalium
• 1997 I. Wilmut cloned Dolly the Sheep
• 2000 Alain Fischer - first successful gene
  therapy trial
• 2003 Complete human genome sequenced