Unit 3 Molecular Genetics
CHAPTER 6
LESSON 1 DNA STRUCTURE
DNA Structure
 Composed of nucleotides
 Deoxyribose sugar
 Phosphate group
 Nitrogenous base
o Adenine
o Thymine
o Guanine
o Cytosine
o Uracil
DNA Bonding
 Phosphodiester bonds join sugar and phosphate group
 Sugar-phosphate backbone
 Glycosidic bonds join nitrogenous base to sugar
 Recall: glycosidic bond: a bond that attaches a sugar to another group that may or may
not be another carbohydrate
Base Pairing
 Adenine and Thymine (2 hydrogen bonds)
 Guanine and Cytosine (3 hydrogen bonds)
 Chargaff’s Rule: In DNA A is equal to the amount of T and G is equal to the amount of C
DNA Structure
 Antiparallel strands
 Running in opposite directions
 5’ end aligns with 3’
 Arranged as a double helix
Complementary Sequences
If you know the sequence of one strand, you can determine the sequence of the complementary
strand.
DNA Terminology
 Histones: structural proteins
 Nucleosomes: Section of DNA wrapped around histones
 Chromatin: DNA + histones
 Chromatid: when a chromosome replicates, there are TWO chromatids
 Centromere: sequence of DNA where the sister chromatids are held together
 Chromosomes: highly condensed chromatin

Gene: A section of DNA that codes for a specific protein
LESSON 2 STRUCTURE AND FUNCTION
Hereditary Molecule
 1868 Swiss Physician Frederick Miescher
 People knew there was inheritance but did not know how
 Isolated a substance from the nucleus  “nuclein”
 Nuclein was acidic and had a large amount of phosphorus
Frederick Griffith
 1928 pneumonia epidemic in Europe
 Two strains of pneumonia:
o S-strain is virulent, with smooth capsule  produce smooth colonies
o R-strain is not without smooth capsule  form rough, irregular colonies
 Heat-killing S-strain bacteria would make it non-virulent  destroys capsule and kills the
bacteria
 Mixing the heat-killed S-strain bacteria with the live R-strain led to virulence
 Suggested something from the heat-killed strain was picked up by the R-strain
 What was the transforming factor? Protein or DNA??
Avery, McLeod, and McCarty: 1944
 Streptococcus bacteria  S-strain and R-strain
 Heat killed S-strain and treated 3 different samples with an enzyme that either destroys
protein, DNA or RNA
 Samples with destroyed DNA did not lead to disease
 They were apprehensive to publish as proteins were the accepted genetic material at the
time. Also, not 100% sure that all proteins were destroyed by enzymatic treatment
Hershey and Chase: 1952
 E. coli and T4 bacteriophage (virus that infects bacteria)
 Two samples: Radiolabelled phosphorus (32P) that labelled DNA (not a lot of
phosphorus in protein)
 Radiolabelled sulfur (35S) that labelled protein as there is not sulfur in DNA
 Infected bacteria with each sample and found the bacteria contained radiolabelled sulfur
Chemical Composition of DNA
 Each DNA molecule contained: deoxyribose sugars, phosphate groups and nitrogenous
bases
 Nucleotide: nitrogenous base attached to one deoxyribose sugar, which is connected to a
phosphate group
 1949: four nitrogenous bases identified:
o Purines: a class of nitrogenous bases with a double-ring structure  adenine and
guanine

o Pyrimidines: a class of nitrogenous bases with a single-ring structure  thymine
and cytosine
1950: Chargaff discovered that ratios of thymine and adenine were always the same in an
organism and that cytosis and guanine were always the same.
Wilkins and Franklin
 Worked in same lab but didn’t get along so they worked independently
 Wilkins used crystallography to determine DNA’s helical shape  poor samples so
Franklin didn’t buy it
 Franklin had much purer samples and produced an X-ray imagine in the shape of an X
 Franklin:
o Suggested that the sugar-phosphate backbone of DNA faced the outside of the
molecule
o Predicted that DNA was a double helix that rotated clockwise
o Determined it had a diameter of 2 nm and one turn was 3.4 nm in length
o Could not figure out how the nitrogenous bases were associated in the center 
hesitant to publish
Watson and Crick; 1952
 1952: Built model using other’s findings
 Wilkins released details of Franklin’s research behind her back
 Each strand consists of a sugar-phosphate backbone
 The nitrogenous bases were attached to the backbone and directed toward the centre of
the molecule
 Strands twisted around each other in clockwise manner
 Each nitrogenous base on one strand is hydrogen bonded with a nitrogenous base on the
other strand.
 Molecule is stable with strands running antiparallel:
o One strand must have the 3’ carbon attached to the deoxyribose sugar at one end
and the phosphate attached to the 5; carbon of the last sugar at the other end
o Other strand must wind around the first strand with its 5’ end opposite the 3’ end
of the first strand
 Thymine and adenine have two hydrogen bonds
 Cytosine and guanine have three hydrogen bonds
LESSON 3 DNA REPLICATION AND REPAIR
When it occurs
 Occurs during interphase, specifically the S phase
Semi-conservative Replication
 DNA replicates in a semi-conservative way. Where we have the double strand DNA, one
original strand is kept after first cycle of replication (2 double strands of DNA made, each
with a original or parent strand and a complimentary or daughter strand)
 The parental strands unwind/separate


Each parental strand is a template
New DNA molecule has one parent strand and one daughter strand
Process of replication
1. Separation
2. Building
3. Proofread and Repair
Step 1: Strand Separation
 DNA strands must be unwound from each other
 Specific sequences act as markers for starting points  replication origins. High AT
content
 In eukaryotes there are many origins due to length of chromosomes
 This creates a Y-shape  replication fork
Replication Bubbles
 An origin will open up in both directions  creating a bubble
 Each bubble expands until it meets and merges with another bubble  two separate
daughter strands
Helicase: enzyme that binds to the origins  separates and unwinds the DNA strands by
breaking the hydrogen bonds between the complimentary base pairs
Helicase can unwind DNA in both directions from the origin with new complimentary DNA
being laid
SSBs
Single-stranded binding proteins (SSBs): enzymes that binds to parent DNA strand to prevent
reannealing of the strands once they have been separated by helicase.
Topoisomerase (Gyrase): enzymes that relieve tension caused by the unwinding of DNA 
cleave one or two of the DNA strands allowing the strands to untwist and the rejoin the strands
Replication Rate
In eukaryotes  50 bp/second
Entire genome in a month if only one replication fork!
1 hour in reality
Step 2: Building Complimentary Strands
RNA primase lays down primer at 3 prime end (of parent strand), uses DNA sequence to build
complimentary RNA.
RNA Primase: Enzyme that builds a small complimentary RNA segment on the strand at the
beginning of the replication fork.
RNA Primers: the short RNA sequences that act as a starting point for replication.
DNA Pol III extends from the primer and starts to lay down DNA. Moves from a 5 to 3
direction.
DNA Pol III need to be primed but RNA primase does not. It cannot start DNA it can only
continue.
Nucleotides are added to 3’ end of growing daughter DNA strand. New strands are assembled in
5-3 strand direction.
Nucleoside Triphosphates are added  for energy, removal of two phosphates, needed for DNA
synthesis.
Phosphodiester bonds are created between the sugar and phosphate. Phosphate (remaining one0
and hydroxyl group on the 3’ carbon at the 3’ end of the growing DNA strand (releasing energy)
Hydrolysis: cleaves the two phosphates (releasing energy)
Phosphates that were released are hydrolysed into organic phosphate.