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DNA: (Deoxyribonucleic
Acid)
The Genetic material
of all living organisms
 Inheritance has its molecular
basis in the precise replication
and transmission of DNA from
parent to offspring.
Was first discovered by
Frederick Meissner (german
physician) in 1860s while he
was changing puss covered
wound dressings
1928:Frederick Griffith
• Performed experiments which
provided evidence that genetic
material is a particular
chemical
• Griffith was trying to find a
vaccine against Streptococcus
pneumoniae( bacteria that
causes pneumonia)
Griffiths Experiment
• Experiment: inject live S strain
into mice
• Results: mice die
• Conclusion: strain is pathogenic
Griffiths Experiment
• Experiment: inject mice with
live R strain
• Results: mice live
• Conclusion: R strain not
pathogenic
Griffiths Experiment
• Experiment: Inject mice with
heat-killed S strain
• Results: mice live
• Conclusion: heat kills bacteria
and it is no longer pathogenic
Griffiths Experiment
• Experiment: mix heat killed S strain
with live R strain
• Results: mice die
• Conclusion: something chemical in
nature moved from the S strain to
the R strain making it pathogenic
History
• By the 1940s, scientist
know that chromosomes
carried hereditary
material that consisted of
DNA and protein.
• Most researchers thought
that protein was the
genetic material
• 1944 Demonstrated that DNA
alone from virulent bacterium
can transform nonvirulent
bacterium.
• Provided more evidence that
DNA is genetic material came
from studies of bacteriophages
( virus that infects bacteria)
• 1947 Developed
Chargaffs rule of
pairing
nucleotides:
• Adenine---Thymine
• Cytocine----Guanine
Watson and Crick built a scale
model of a double helix that
would conform to data and
known chemistry of DNA
They proposed a ladder-like
molecule that twisted into a
spiral ( double helix), with sugar
and phosphate backbones and
nitrogen base pairs as rungs of
the ladder
In April 1953, Watson and Crick’s new
model of DNA structure was published
in the British Journal of Nature.
This model for the DNA structure
suggested a template mechanism for
DNA replication…and was called a
semiconservative model for DNA
replication
semiconservative model for DNA
replication
• Watsons and Crick’s model suggested:
1. The 2 DNA strands separate
2. Each strand is a template for assembling a
complementary strand
3. Nucleotides line up along the template
according to base pairing rules
4. Enzymes link the nucleotide together
5. Each new DNA strand has one old and one
new strand
• Rosalind Franklin's x-ray diffraction work
gave Watson and Crick the key to
unlocking the structure of DNA.
• She died before she could receive
appropriate recognition of her contribution.
She did not receive the Nobel Prize (not
administered posthumously).
Martha Chase & Alfred Hershey
(1952)
Martha Chase & Alfred
Hershey (1953)
Find that only DNA from
virus enters cells and
directs reproduction of
new viruses
The Meselson - Stahl Experiment
1958
"DNA Replication is Semiconservative
•
They proposed that when the time came
for DNA to be replicated, the two strands
of the molecule:
1. separated from each other but
2. remained intact as each served as the
template for the synthesis of
3. a complementary strand.
• When the replication process is complete,
two DNA molecules — identical to each
other and identical to the original — have
been produced
History
• DNA
– Comprised of genes
– In non-dividing cell
nucleus as chromatin
• Protein/DNA complex
– Chromosomes form
during cell division
• Duplicate to yield a full set
in daughter cell
History
• DNA
• The 5 carbon sugar
(PENTOSE) is
Deoxyribose
• It is double stranded
• DNA is found in the
nucleus of the cell
• Composed of sugar,
phosphate and nitrogen
base pairs
DNA is a Double Helix
• Nucleotides
– A, G, T, C
• Sugar and phosphate
form the backbone
• Bases lie between the
backbone
• Held together by
H-bonds between the
bases
– A-T – 2 H bonds
– G-C – 3 H bonds
H - Bonds
• Base-pairing rules
– AT only (AU if DNARNA hybrid)
– GC only
• DNA strand has
directionality – one end is
different from the other end
• 2 strands are anti-parallel,
run in opposite directions
– Complementarity results
– Important to replication
Helical Structure
Nucleotides as Language
• We must start to think of the
nucleotides – A, G, C and T as part
of a special language – the
language of genes that we will see
translated to the language of
amino acids in proteins
Genes as Information Transfer
• A gene is the sequence of nucleotides
within a portion of DNA that codes for a
peptide or a functional RNA
• Sum of all genes = genome
• DNA
collected
from cheek
cells
General mechanism of DNA
replication is conceptually
simple, but the actual process
is complex.
DNA Replication
• Semiconservative
• Daughter DNA is a
double helix with 1
parent strand and 1
new strand
• Found that 1 strand
serves as the
template for new
strand
DNA Template
• Each strand of the parent DNA is used as a
template to make the new daughter strand
• DNA replication makes 2 new complete double
helices each with 1 old and 1 new strand
•
•
•
•
•
Step 1: Origin of replication
Step 2: Strand separation
Step 3: Priming
Step 4: Synthesis of new DNA Strand
Step 5: Proof reading
Steps 3 and 4 happen simultaneously
DNA replication begins at a special
site call the origin of replication
The ‘DNA double helix open at the
origin and replication forks spread
in both directions away from the
central initiation point creating a
replication bubble.
Replication Origin
• Site where replication
begins
– 1 in E. coli
– 1,000s in human
• Strands are separated to
allow replication machinery
contact with the DNA
– Many A-T base pairs
because easier to break 2
H-bonds that 3 H-bonds
• Note anti-parallel chains
When DNA replicates, many different
proteins work together to accomplish
the following steps:
The two parent strands are unwound
with the help of DNA helicases ( an
enzyme).
• Single stranded DNA binding
proteins attach to the unwound
strands, preventing them from
winding back together.
• Topoisomerase: Is another protein
that serves to relieve the stress and
untangle any kinks or snarls in the
DNA
• The strands are held in position,
binding easily to DNA polymerase,
which catalyzes the elongation of the
leading and lagging strands. (DNA
polymerase also checks the accuracy
of its own work!).
• All is according to the base-pairing
rule
• While the DNA polymerase on the
leading strand can operate in a
continuous fashion, RNA primer is
needed repeatedly on the lagging
strand to facilitate synthesis of Okazaki
fragments.
•
• DNA primase, which is one of several
polypeptides bound together in a group
called primosomes, helps to build the
primer.
• A primer is a short segment of RNA
made by an enzyme called primase
• Finally, each new Okazaki fragment is
attached to the completed portion of
the lagging strand in a reaction
catalyzed by DNA ligase.
• There are more than 50 different types
of DNA repair enzymes, but most
perform 1 of 2 different types of repair.
• 1. Directly reversing the change.
• 2. Excision repair: The damage
segment is excised by one repair
enzyme and the remaining gap is filled
in by base-pairing nucleotides
• Legend:
DNA and RNA transcription video - real time DNA encoding pr
• http://DNA and RNA transcription
video - real time DNA encoding pr YouTube
Transcription and translation are the
means by which cells read out, or
express, the genetic instructions in
their genes.
Because many identical RNA copies
can be made from the same gene, and
each RNA molecule can direct the
synthesis of many identical protein
molecules, cells can synthesize a large
amount of protein rapidly when
necessary
Transcription begins with the opening
and unwinding of a small portion of the
DNA double helix to expose the bases
on each DNA strand.
One of the two strands of the DNA
double helix then acts as a template for
the synthesis of an RNA molecule.
As in DNA replication, the nucleotide
sequence of the RNA chain is
determined by the complementary
base-pairing between incoming
nucleotides and the DNA template.
• Unlike a newly formed DNA strand, the
RNA strand does not remain hydrogenbonded to the DNA template strand.
Instead, just behind the region where
the ribonucleotides are being added,
the RNA chain is displaced and the
DNA helix re-forms.
• Thus, the RNA molecules produced by
transcription are released from the DNA
template as single strands.
• The enzymes that perform transcription
are called RNA polymerases
• Transcription begins when the enzyme
RNA polymerase binds to the
promoter,( a specific nucleotide
sequence ) located in the DNA at the
start end of the gene and continues
until a terminator code is reached.
• Translation is a process where genetic
information is translated from a ``nucleic
acid language" to an "amino acid
language".
• Translation is catalyzed by a large enzyme
called a ribosome, which contains proteins
and ribosomal RNA (rRNA).
• Translation also involves specific RNA
molecules called transfer RNA (t-RNA)
which can bind to three basepair
codons on a messenger RNA (mRNA)
and also carry the appropriate amino
acid encoded by the anticodon ( tRNA).
• The ribosome assembles on the first
AUG (start codon) in the mRNA. This
codon encodes the amino acid
methionine (Met).