The Structure & Function of DNA

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The Structure Function of DNA

• Chapter 10

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• Molecular biology the study of heredity at the
  molecular level
• All organisms use the same genetic code for
  translation and transcription and also for
  replication

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Biology and SocietySabotaging HIV

• AIDS, acquired immunodeficiency syndrome - one of
  the most significant health challenges facing the
  world
• - infected 40 million worldwide with 3 million
  deaths
• - cause of AIDS is infection by the HIV, human
  immunodeficiency virus
• - no cure for AIDS but can be slowed by anti-HIV
  drugs
• AZT (azidothymidine), the most effective drug at
  preventing the spread of HIV
• - how does AZT stop HIV?

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AZT and the T Nucleotide

• Viruses cannot reproduce on their own they must
  infect a host cell
• - HIV depends on a viral enzyme to convert its
  RNA genome into a molecule of DNA
• - the viral enzyme (reverse transcriptase) uses
  nucleotides (A,T,C,G) from the cytoplasm of the
  infected cell to build a DNA molecule
• - AZT is so similar to the T (thymine)
  nucleotide it can bind to the viral enzyme
  instead of T (shape and function)
• - but AZT cannot be incorporated into a growing
  DNA chain, interferes with the synthesis of HIV
  DNA

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Figure 10.1
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DNA Structure and Replication

• DNA was known to be a chemical in cells by the
  end of the 19th century
• - Mendel and other early genetists did all their
  work without knowledge of DNA
• In the late 30s, experimental studies convinced
  most biologist that a specific molecule was the
  basis of inheritance
• - by the 40s scientists knew that chromosomes
  consisted of 2 types of chemicals DNA and
  protein
• - in the early 50s experimental discoveries had
  convinced the scientific world that DNA acts as
  the hereditary material

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• Scientist had identified all its atoms and how
  they were covalently bonded to one another
• Scientist understood the unique properties of DNA
  
• - has the capacity to store genetic information
• - can be copied and passed from generation to
  generation
• What was not understood was the 3-dimensional
  structure

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DNA and RNA Structure

• Both DNA and RNA are nucleic acids
• - consist of chains (polymers) of subunits
  (monomers) called nucleotides
• - the nucleotides are joined together by
  covalent bonds between the sugar of one
  nucleotide and the phosphate of the next (a
  sugar-phosphate backbone)
• The 4 nucleotides found in DNA differ in their
  nitrogenous bases
• - thymine (T), cytosine (C), adenine (A), and
  guanine (G)
• RNA has uracil (U) in place of thymine

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Figure 10.2

• A molecule of DNA contains 2 polynucleotides
• Each nucleotide consists of a nitrogenous base, a
  sugar (blue), and a phosphate group (gold)

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• The phosphate group with a P atom at its center,
  is the source of the acid in nucleic acid
• - the phosphate has given up a hydrogen ion
  (H), leaving a negative charge on one of its
  oxygen atoms
• The sugar has 5 carbon atoms 4 in its ring and
  one extending above the ring
• - the ring also includes an oxygen
• - the sugar is deoxyribose because it is missing
  an oxygen atom (compared to ribose in RNA)
• The nitrogenous base has a ring of nitrogen and
  carbon atoms with various functional groups
• - nitrogenous bases are basic

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Deoxyribonucleic Acid

• The 4 nucleotides found in DNA differ only in
  their nitrogenous bases there are 2 types
• - thymine (T) and cytosine (C) are single-ring
  structures
• - adenine (A) and guanine (G) are double-ring
  structures
• RNA ribonucleic acid
• - has the nitrogenous base uracil (U) instead of
  T
• - contains ribose instead of deoxyribose

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Fig 10.3b

• Watson and Crick used X-ray crystallography data
  from Rosalind Franklin to reveal the basic DNA
  shape
• While in John Randalls lab Franklin had
  discovered that DNA could crystallize into two
  different forms, an A and a B form

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• Watson and Crick are shown in 1953 with their
  model of the double helix
• In 1962 Watson, Crick, and Wilkins received the
  Nobel Prize for their work

Figure 10.3a
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Fig 10.4

• A rope-ladder model of a double-helix. The ropes
  at the sides represent the sugar-phosphate
  backbones.
• Each wooden rung stands for a pair of bases
  connected by H bonds

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Fig 10.5

• Bases pair in a complementary fashion
• Bases hydrogen bond to each other
• DNA strands in a double helix are antiparallel
  the 2 sugar-phosphate backbones are oriented in
  opposite directions

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DNA Replication

• When a cell or whole organism reproduces, a
  complete set of genetic instructions must pass
  from one generation to the next
• Watson and Cricks model for DNA suggested that
  DNA replicates by a template mechanism
• - each DNA strand serves as a mold or template,
  to guide reproduction of the other strand
• - if you know the sequence of bases in one
  strand of the double helix, you can determine the
  sequence of bases in the other strand by applying
  the base-pairing rules

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• The 2 strands of the original (parental) DNA
  molecule (blue) serve as templates for making new
  (daughter) strands (orange)
• Replication results in 2 daughter DNA molecules,
  each consisting of one old strand and one new
  strand
• The parental DNA untwists as its strands
  separate, and the daughter DNA rewinds as it forms

Figure 10.6
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DNA Replication

• The nucleotides are lined up one at a time along
  the template strand in accordance with the
  base-pairing rules
• - enzymes link nucleotides to form the new DNA
  strands
• - the completed new molecules, identical to the
  parental molecule, are known as daughter DNA
  molecules
• DNA polymerases enzymes that make the covalent
  bonds between the nucleotides of a new DNA strand
• - as an incoming nucleotide base-pairs with its
  complement on the template strand, a DNA
  polymerase adds it to the end of the daughter
  strand

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• DNA replication proceeds at a rate of 50
  nucleotides per second
• - only about one in a billion incorrectly pair
• DNA polymerases and some associated proteins are
  also involved in repairing damaged DNA
• - DNA can be damaged by toxic chemicals, by
  high-energy radiations such as X-rays and
  ultraviolet light

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• Damage to DNA by UV Light
• The UV radiation in sunlight can damage the DNA
  in skin cells
• Fortunately, cells can repair some of the damage
  use some of the same enzymes that catalyze the
  replication of DNA
• Protect your skin - use sunscreen and protective
  clothing

Fig 10.7
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• DNA replication begins at specific sites or
  origins of replication on a double helix
• - proceeds, creating replication bubbles
• - parental DNA strands open up as daughter
  strands elongate on both sides of each bubble
• - a DNA molecule of a eukaryotic chromosome has
  many origins where replication can start
  simultaneously
• - eventually all the bubbles merge, yielding 2
  completed double-stranded daughter DNA molecules
• DNA replication ensures that all the body
  (somatic) cells carry the same genetic
  information
• - also the means by which genetic information is
  passed along to offspring

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Figure 10.8
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Checkpoint

• Compare and contrast the chemical components of
  DNA and RNA
• Along one strand of a DNA double helix is the
  nucleotide sequence AAGTGTAAC. What is the
  sequence for the other DNA strand?
• How doe complementary base pairing make the
  replication of DNA possible?
• What is the function of DNA polymerase in DNA
  replication?

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Answers

• Both are polymers of nucleotides a nucleotide
  consists of a sugar a nitrogenous base a
  phosphate group. In RNA the sugar is ribose, in
  DNA the sugar is deoxyribose. RNA uses uracil (U)
  and DNA thymine (T)
• AAGTGTAAC TTCACATTG
• When the 2 strands of the double helix separate,
  each serves as a template complementary strands
• This enzyme convalently connects nucleotides one
  at a time to one end of a growing daughter strand
  as the nucleotides line up along a template
  strand according to the base-pairing rules

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The Flow of Genetic Information from DNA to RNA
to Proteins

• How does DNA function as the inherited directions
  for a cell or organism?
• What are the instructions and how are these
  instructions carried out?

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How an Organisms Genotype Produces Its Phenotype

• An organisms genotype, its genetic makeup, is
  the sequence of nucleotide bases in its DNA
• The phenotype is the organisms specific traits
• - arise from the actions of a wide variety of
  proteins
• - examples include enzymes that catalyze
  metabolic reactions and structural proteins that
  provide the infrastructure for the body of an
  organism

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• DNA specifies the synthesis of proteins but a
  gene cannot build a protein directly
• - dispatches instructions in the form of RNA
  (mRNA)
• - mRNA programs protein synthesis
• - molecular chain of command is from DNA in
  the nucleus to RNA to protein synthesis in the
  cytoplasm
• The 2 main stages are
• - Transcription, the transfer of genetic
  information from DNA into an RNA molecule
• - Translation, the transfer of the information
  in the RNA into a protein

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• Relationship between genes and enzymes came in
  the 40s
• - from the work of George Beadle and Edward
  Tatum with the orange bread mold Neurospora
  crassa
• - studied strains of the mold that were unable
  to grow on the usual growth medium
• - these strains lacked an enzyme in a metabolic
  pathway that produced a molecule the mold needed
• - they were able to show that each mutant was
  defective in a single gene

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• Beadle and Tatum hypothesis one gene-one
  enzyme
• Has since been modified to include all types of
  proteins
• The one gene one polypeptide hypothesis states
  that the function of an individual gene is to
  dictate the production of a specific polypeptid

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Figure 10.9
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From Nucleotides to Amino Acids An Overview

• Genetic information in DNA is transcribed into
  RNA then translated into polypeptides
• - how is the chemical language of DNA translated
  into the different Chemical language of
  polypeptides?
• Both DNA and RNA are polymers of nucleotides
  strung together in specific sequences that convey
  information
• - specific sequences of bases each with a
  beginning and an end, make up the genes on a DNA
  strand
• - a typical gene consists of 1000s of
  nucleotides and a single DNA molecule may contain
  1000s of genes

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• A segment of DNA is transcribed into an RNA
  molecule
• - the process is called transcription because
  the nucleic acid language of DNA has been
  rewritten into RNA
• - RNA was synthesized using the DNA strand as a
  template, the nucleotide bases of the RNA
  molecule are complementary to those on the DNA
  strand
• Translation is the conversion of the nucleic acid
  language to a polypeptide language
• - the monomers of polypeptides are the 20 amino
  acids common to all organisms
• - the message is written in a linear sequence of
  mRNA
• - sequence of nucleotides of the RNA molecule
  dictates the sequence of amino acids

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• Rules for translation of a RNA message into a
  polypeptide
• - there are only 4 different kinds of
  nucleotides in DNA (A,G,C,T) and RNA (A,G,C,U)
• - if each nucleotide base coded for one amino
  acid, only 4 amino acids could be constructed
• - triplets of bases or codons are the smallest
  words that can specify all the amino acids
• - 43 64 possible code words (more than 20)
• - redundancy of the code, more than one codon
  can code for an amino acid
• One DNA codon (3 nucleotides) ? one RNA codon (3
  nucleotides) ? one amino acid

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• A segment from a strand of gene 3 - sequence of
  bases
• The red strand represents the results of
  transcription an RNA molecule its base
  sequence is complementary to that of the DNA
• The purple chain represents the results of
  translation a polypeptide

Brackets indicate that 3 RNA nucleotides (a
codon) code for each amino acid
Figure 10.10
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Figure 10.11