DNA STRUCTURE AND REPLICATION

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DNA STRUCTURE AND REPLICATION
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HISTORY

• 1869 Friedrich Miescher discovered DNA in
  nucleus
• 1909 Archibald Garrod lack of inheritance of
  certain proteins. Proteins are genetic material
• 1928 Fredrich Griffith Identified DNA as
  source of genetic material using bacteria
• 1930s Oswald Avery, Colin MacLeod and Maclyn
  McCarty Confirmed DNA
• 1950 Alfred Hershey and Martha Chase confirmed
  DNA is biochemical of heredity

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Hershey and Chase
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HISTORY of STRUCTURE

• 1909 Phoebus Levene Identified ribose and
  1929 identified deoxyribose and determined
  nucleotide structure
• Early 1950s
• Erwin Chargoff - Equal numbers of A T and C
  G
• Maurice Wilkins and Rosalind Franklin x-rayed
  DNA to show repeating nucleotide structure

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Rosalind Franklin
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HISTORY of STRUCTURE

• 1953 James Watson and Francis Crick combined
  data to create a 3-D model of structure called
  the double helix

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Watson and Crick
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DNA STRUCTURE

• DNA displays anti-parallelism 2 chains of
  nucleotides run opposite to each other in a head
  to tail relationship
• 3 to 5 direction vs. 5 to 3 direction

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DNA STRUCTURE
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VOCABULARY

• Deoxyribonucleic acid DNA chain of
  nucleotides
• Chromosomes DNA wrapped around proteins called
  histones
• Nucleosomes DNA and histones wrapped in
  bead-like structure
• Chromatin active form of chromosomes

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DNA STRUCTURE
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DNA STRUCTURE
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DNA STRUCTURE

• DNA deoxyribonucleic acid
• Stores and transmits genetic information needed
  for all cell functions
• Polymer consisting of 1000s of nucleotides
• Nucleotide
• 5 carbon sugar deoxyribose
• Phosphate group
• 1 of 4 nitrogen bases

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DNA STRUCTURE
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DNA STRUCTURE

• Nitrogen Bases
• Adenine
• double ringed purines
• Guanine
• Thymine
• single ringed pyrimidines
• Cytosine

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NITROGEN BASES
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DNA STRUCTURE

• Structure of DNA is double strand of covalently
  bonded nucleotides in twisted ladder shape
  double helix
• Sides of ladder sugar phosphate groups
• Rungs of ladder nitrogen bases

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DNA STRUCTURE
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DNA STRUCTURE

• Bases are paired together in specific manner
  Base pairing rule
• Adenine only pairs with Thymine
• Guanine only pairs with Cytosine
• Bases held together in rungs by weak hydrogen
  bonds
• 2 hydrogen bonds between A T
• 3 hydrogen bonds between C G
• The structure of DNA and sequence of bases
  determines its function

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DNA STRUCTURE
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DNA REPLICATION

• Why does DNA make copies of itself?
• To pass genetic information on to new generations
  of cells
• Replication begins when a helicase break the
  hydrogen bonds between bases at initiation sites
• Helicase is an enzyme that unwinds DNA and holds
  the strands apart during replication

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DNA REPLICATION

• RNA polymerase attracts RNA nucleotides to build
  RNA primer at initiation site
• RNA primer attracts DNA polymerase
• DNA polymerase enzyme that pairs up free
  nucleotides with exposed complementary bases on
  each strand and proof reads the new strand

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DNA REPLICATION

• Ligase enzymes help nucleotides bond, forming one
  new strand on each original strand
• Called semi-conservative replication
• Original strand acts as template
• Each DNA replicates at 100s of points
  simultaneously, then the sections rejoin
• Open portions are called replication forks

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DNA REPLICATION
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DNA REPLICATION

• Occurs in 5 to 3 direction
• Continuous replication in one direction this is
  the leading strand.
• Replication in lagging strand occurs in segments
  called Okazaki fragments.

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DNA REPLICATION
Okazaki fragment
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DNA MUTATIONS AND REPAIR

• Replication of DNA is very accurate
• Mistakes only occur 1 in 100,000 bases
• Polymerase corrects errors found

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Mutation and Repair

• Dimers
• U-V radiation causes covalent bonds to form
  between adjacent pyrimidines
• Causes kinks in chain insertion of
  non-complementary bases
• Photoreactivation enzyme photolyase breaks the
  dimer with energy from blue light

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Mutation and Repair

• Excision repair
• Cutting of bond between deoxyribose and base to
  remove dimers
• DNA polymerase fills in correct nucleotides
• Mismatch repair
• Enzymes proofread loops in DNA to show inaccurate
  alignment
• Mismatches occur in short repeating segments
  called microsatellites

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THYMINE DIMER