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Chapter 9

DNA: The Molecule of Heredity

What is DNA?

Answer: Molecule that carries the blueprint of life

General Features:

• DNA is packages in chromosomes (DNA + Proteins)

• Gene = Functional segment of DNA located at a particular place on a chromosome

Ge

ne

Chromosome

Discovery of nucleic acid

• 1869: Miescher

�isolated DNA from pus!

• DNA is made up of:

�Deoxyribose : the sugar

�Phosphate

�nitrogen rich base

What is the genetic material?

• Protein vs DNA

�Debated until the 1950’s.

• Protein complex

�20 different amino acids

�Forms thousands of different

molecules.

• DNA simple

�Only 4 nucleotides

Lactase

Genetic material = DNA

• Two major experiments

� 1920’s -1950’s

1. Griffith’s dead mice

2. Radioactively labelledbacteriophages

� Bacteriophages are viruses that destroy bacteria. Typical bacteriophage

infecting a bacteria cell

Griffith’s mice experiment

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(Figure 9.1)

Second experiment: radioactive viruses

• Viruses have protein coats, which

enclose DNA or RNA.

�Only DNA viruses was used in this

experiment.

• The proteins were labelled with

radioactive sulfur, the DNA was

labelled with radioactive

phosphorus.

Electron microscope

photos of bacteriophages.

virus particlelabeled with 35S

DNA (blue)being injected

into bacterium

35S remainsoutside cells

virus particle

labeled with 32P

DNA (blue)

being injected into bacterium

35P remains

inside cells

Structure of DNA:

• Nucleic acid composed of individual nucleotides

Deoxyribose

Know this structure, you will see it on the exam!

Structure of DNA:

• 4 types of nucleotides (nitrogen base differences):

Purines (double-ring bases) Pyrimidines (single-ring bases)

• Nucleic acid composed of individual nucleotides

How are the Nucleic Acids arranged to form DNA?

1) Chargaff (1949):

• DNA contains equal amounts of adenine and thymine

• DNA contains equal amounts of cytosine and guanine

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How are the Nucleic Acids arranged to form DNA?

• Rosalind Franklin and Maurice Wilkens (early 1950s):

� Used X-ray diffraction

• DNA is a helical molecule (corkscrew)

• DNA has a uniform diameter (2 nm)

• DNA consists of repeating sub-units

How are the Nucleic Acids arranged to form DNA?

• Watson and Crick (1953)

� DNA is two separate strands of linked nucleotides

� Phosphate groups bonded to sugar groups (backbone)

� Antiparallel (strands opposite one another)

(similar to Figure 9.5)

The order of nucleotides in DNA can encode vast amountsof information:

• 10 nucleotides = > 1,000,000 possible sequences

• Organisms have millions (bacteria) to billions (plants / animals) of nucleotides�Humans have 3 BILLION nucleotides.

• The copying of DNA is a critical event in a cell’s life

• Cell reproduce by mitosis to produce two daughter cells from a single parental cell

• Each daughter cell must receive an exact copy of DNA

• DNA replication produces two DNA double helices throughprocess termed semiconservative replication

DNA Replication

• Parental strands unwind and separate

• Daughter strands are formed using parental strands as templates

• Parental strand and new daughter strand wrap togetherto form new double helix

Semiconservative Replication:

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Semi-conservative replication

Step 1: DNA Strand Separation

• DNA Helicase (enzyme) breaks hydrogen bondsholding nitrogen bases together (unzips)

� Requires energy (ATP)

DNA Replication - A Closer Look...

� Multiple DNA helicases work on single chromosome

� form replication bubbles; time-saving mechanism

DNA Helicase

DNA Replication - A Closer Look...

Step 2: DNA Synthesis

• DNA Polymerase (enzyme) joins nucleotide sub-unitsto form new strands of DNA

� Forms complementary strands to parent strands

(Recognizes nucleotide and adds appropriate base)

T AC

A TG C

T GC A

G

A

AT G G A T

G

T

A TC C TC A

Polymerase

DNA Replication - A Closer Look...

Step 2: DNA Synthesis

• DNA Polymerase (enzyme) joins nucleotide sub-unitsto form new strands of DNA

� Forms complementary strands to parent strands

(Recognizes nucleotide and adds appropriate base)

• DNA Polymerase can only move in one direction

� One strand synthesized as continuous molecule

� Second strand synthesized in small pieces

DNA

PolymeraseDNA Ligase: Attaches pieces together

DNA replication movie

• DNA movie

• DNA replication is a rapid process

• 700 nucleotides / second

• DNA polymerase mismatches 1 bp / 10,000 bps

• Proof-reading enzymes correct mistakes

• Overall mistake rate = 1 bp / 1,000,000,000 bps

�Mutations

DNA Replication - Mistakes Happen...

• Other hazards damage DNA

• Body temperature = 98.6 °F = 10,000 bp lost / day

• Ultraviolet light

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1st Degree

2nd Degree

3rd Degree

Sun Burns:

UV light from sun damages DNA

If damage is great enough,

cell will commit cellular suicide

BUT…If the damage is in region of DNAcontrolling replication, cancer may result

AB

CD

symmetryorder (irregular)

olor (irregular)iameter (large)

What happens if we don’t have the DNA repair enzymes?

Xeroderma pigmentosum: a skin cancer

predisposition disease.

Extreme sensitivity to sunlight >> skin cancer

DNA damage due to sunlight

Probability of cancer

Cause: genetic defects in the enzyme

that repairs sunlight damage.

Xeroderma pigmentosum

• Possible inspiration for vampire myths.

�Patients with XP develop lesions when exposed to sunlight.

�Autosomal recessive

�Both parents must be carriers.

�Only treatment is avoidance of UV light sources.