1953: James Watson and Francis Crick create double helical model for DNA

After Morgan showed genes are located on chromosomes, it sparked the debate of

DNA and protein being the candidates for the genetic material

Much was known about proteins

o Had great heterogeneity and specificity of function

Essential for the hereditary material

Little was known about nucleic acids

o Their chemical and physical properties seemed to uniform to account for the

multitude of inherited traits

Frederick Griffith: 1928 British Medical Officer

o Studied streptococcus pneumoniae- pneumonia causing bacteria

o Had two strains- a pathogenic and a harmless

o When he killed the pathogenic strain with heat and mixed with the harmless

strain , some cells transformed into pathogenic cells

Transformation: a change in genotype and phenotype due to

assimilation of external DNA by a cell

Oswald Avery: 1944 American Bacteriologist

o Built on Griffith’s work and proved that DNA was the responsible agent for

transformation

o Colleagues: Maclyn McCarty and Colin MacLeod

o Experiment: Separate each part of the bacteria and test one by one

o Skepticism arose because not much was known about DNA

Viruses provided additional evidence for DNA as the genetic material

o To reproduce, viruses must infect and take over a cell’s metabolic machinery

o Bacteriophages (phages): Viruses that infect bacteria

1952: Alfred Hershey and Martha Chase

o Showed that DNA was the genetic material of a phage was known as T2

T2 was all DNA and a little protein

Proved that DNA was the genetic material by growing T2 with E. Coli

Two sets of petri dishes were prepped- one with Sulfure-35 to

stain the protein and one with Phosphorous-32 to stain DNA

After letting the T2 and E. Coli mingle, they noticed that the

inside of the E. Coli cells were blue- showing that DNA entered

the cell

Erwin Chargraff: Biochemist

o Analyzed the base composition of the DNA from multiple euakryotes

Noticed that all the four bases (A, C, T, G) were present in eukaryotes,

but in characteristic ratios that varied from eukaryote to eukaryote

Chargraff’s Rule: The amount of Adenine approximately equaled the

amount of Thymine and the amount of Guanine approximately

equaled the amount of Cytosine

Once biologists accepted DNA as the genetic material, they needed to know it’s

structure

o Watson and Crick used X-ray crystallography pictures from Rosalind

Franklin

o Watson was familiar with the types of patterns that helical molecules

produce in X- ray crystallographies

The picture told Watson that the structure was helical and enabled

him to deduce the width of the helix and the spacing of the

nitrogenous bases along it

The width showed that the helix was two stranded

o The crystallography showed that the helix makes one full turn every 3.4

nanometer (nm)

Bases are stacked 0.34 nm apart

10 layers of base pairs in each turn on the helix

o Adenine pairs with Thymine

o Guanine pairs with Cytosine

Purine + Purine= too wide

Pyrimadine + Pyrimadine= too narrow

Purine + Pyrimadine= width consistent with X-ray data

The Watson- Crick model proved Chargraff’s rule

When a cell copies a DNA molecule, each strand serves as a blueprint, demanding

certain nucleotides to make a complementary strand.

o Semiconservative Model: Type of DNA replication in which the replicated

double helix consists of one old strand, derived from the old molecule, and

one newly made strand

Humans have about 6 billion base pairs per cell

o Only takes a few hours to copy all this DNA

o Only a few errors per 1 billion nucleotides

More than a dozen enzymes and proteins participate in DNA replication

DNA replication starts at special sites

o Origins of replication: special sites on DNA where replication starts

o Proteins attach to DNA and begin to unzip the DNA into two strands

o Replication occurs from both top to bottom and bottom to top

simultaneously

o DNA Polymerases: enzymes that catalyze the replication of DNA strands

o Rate of replication is 500 million nucleotides per second

Human replication occurs at 50 million nuecleotides per second

o Nucleoside triphosphates serve as substrates for DNA Polymerase

The two DNA sugar- phosphate backbones run anti-parallel to eachother (parallel

but in opposite

directions)

Picture showing the antiparallel

structure of the DNA Double Helix

Structure

The numbers 3 and 5 refer to the carbons in the the backbone.

Leading Strand: The new continuous complementary DNA strand synthesized

along the template strand in the mandatory 5’3’ direction

Lagging Strand: A discontinuously synthesized DNA strand that elongates in a

direction away from the replication fork

o First synthesized as a series of pigments- known as Okazaki fragments

o Pigments are about 100-200 nucleotides in length

DNA ligase joins the sugar-phosphate backbones of the Okazaki Fragments to create

a single DNA strand

Replication of cellular DNA:

Helicase is an enzyme that untwists the double helix at the replication fork.

Summary of DNA Replication: