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The Central Teaching of
Molecular Biology
• Information flows from
DNA to RNA to PROTEIN
DNA
Translation
RNA
Construction
Transcription
Blue Print
PROTEIN
1DNA
1-DNA
2- Synthesis
of mRNA in
the nucleus
Nucleus
Transcription
3- mRNA
Cytoplasm
Nucleus
Cytoplasm
4- Movement
of mRNA into
cytoplasm via
nuclear pore
mRNA
Ribosome
5- Synthesis
of Protein
6- Polypeptide
Translation
The Genetic Code &
Nucleic Acids
• DNA and RNA are called
Nucleic Acids.
• Nucleic Acids store information in the
form of a molecular language.
• The language or code that is written
into and read from Nucleic Acids is
called the genetic code.
Historical Moments in the
Discovery of Nucleic Structure
Between 1949 and 1953,
Erwin Chargaff analyzed
the nucleotide base
compositions of DNA
molecules found in
human beings and a
number of other
organisms as well.
The four nitrogenous bases in DNA are
adenine (A)
O
NH2
H
N
H
O
N
Purine
H
bases
H3C
N
N
thymine (T)
N
H
N
H
O
NH2
H
N
N
H
Pyrimidine
bases
H
N
H
N
H
N
H
guanine (G)
NH2
O
N
H
H
cytosine (C)
A
T
C
G
What conclusions could you
make from Chargaff’s Data?
Historical Moments in the
Discovery of Nucleic Structure
In 1950, after analyzing the
data, Erwin Chargaff
reported that even though
the DNA composition
varied from one species to
another he suggested that
there was a pairing of
complementary nucleotide
bases (A to T and G to
C) in the DNA molecule.
Historical Moments in the
Discovery of Nucleic Structure
Between 1948 and 1952,
Linus Pauling discovered
the role hydrogen
bonding played in the complex helical
structure of polypeptides and proteins.
His structural discovery, called the
“alpha-helix” earned him the Nobel
Prize for Chemistry for his work on
molecular bonding and structure,
especially in proteins.
Polypeptide
Hydrogen
Bonds
alpha-helix
Protein
Historical Moments in the
Discovery of Nucleic Structure
Between 1950 and 1953,
Rosalind Franklin and
Maurice Wilkins took
x-ray crystallographs
(a form of microscopic
photography) that
showed that the
mysterious molecule DNA had a
spiral shape. They were awarded
Nobel Laureates for their efforts.
Twin
Scaffolding
Sugar
Spirals
Center
Vertical
Axis
Paired Bases
Historical Moments in the
Discovery of Nucleic Structure
In 1953,
James Watson &
Francis Crick put
all the pieces of
“scientific data” together and
unscrambled the complex
chemical structure of DNA for
which they also were awarded
Nobel Laureates.
Watson & Crick’s DNA Model
• Pairing of complementary
nucleotide bases Chargaff
• Base pairs combine
using hydrogen bonds Pauling
• The DNA molecule has a
spiral shape Franklin & Wilkins
• The spiral is a double
alpha-helix Pauling
End of Introduction to the
Central Dogma of Biology
Beginning of the Structure
of Nucleic Acids and DNA
Nucleic Acids are Polymers
•A polymer is a large molecule
consisting of up to millions of
repeated linked molecular units that
are relatively light and simple.
•Each simple molecular unit is called a
monomer
U
T
P
Ds
DNA monomer
P
Rs
RNA monomer
Nucleic Acids are Polymers
• Monomeric units are made up of an
information carrying nitrogen Base
• a sugar Scaffold to hold the base
• a phosphate Connector
Base
Scaffold
Rs
Ds
Connector
P
• Nucleic acids (DNA and RNA) are
composed of 4 different nitrogenous
bases
O
NH2
H
N
A
N
N
H
N
H
N
O
N
H
H
NH2
H
N
H
N
N
C
H
N
T
H
O
G
H3C
N
H
purines
NH2
O
N
H
H
pyrimidines
•Each have H bond
donors and
acceptors
O
NH2
H
N
A
N
N
H
N
H
N
O
N
H
H
NH2
H
N
H
N
N
C
H
N
T
H
O
G
H3C
N
H
purines
NH2
O
N
H
H
pyrimidines
•A-T base pairs form 2 H bonds &
G-C base pairs form 3 H bonds
O
NH2
H
N
A
N
N
H
N
H
N
O
N
H
H
NH2
H
N
H
N
N
C
H
N
T
H
O
G
H3C
N
H
purines
NH2
O
N
H
H
pyrimidines
• In RNA the base Thymine
(T) is replaced by Uracil (U)
NH2
N
A
U
T
N
H
N
H
N
H
NH2
O
H
N
G
H
N
N
C
H
N
N
NH2
H
O
N
H
H
purines
pyrimidines
In DNA the scaffold is 2’-deoxyribose,
a pentose (five carbon) sugar
In RNA the scaffold is ribose, a
pentose (five carbon) sugar
5’
5’
O
OHCH2
4’
H
H
3’
OH
OH
1’
H
H
2’
H
O
OHCH2
4’
H
H
3’
OH
OH
1’
H
H
2’
OH
In both DNA and RNA
the base is connected
to the 1’ position of the
scaffolding sugar *
O
H
O
H 3C
N
N
H
O
5’
OHCH2
4’
H
H
3’
OH
OH
1’
H
H
2’
H
* (liberating water - dehydration synthesis)
H
In both DNA and RNA a
phosphate connector is
O
added to the 5’ position H
of the scaffolding sugar
N
O
5’
O- P O OHCH2
4’
OH
H
3’
OH
O
O
N
O
1’
H
H
2’
H
H 3C
H
nucleoside
A nucleoside is the
chemical combination
of base and sugar.
O
5’
O- P O CH2
4’
OH
H
3’
OH
O
H
O
O
H 3C
N
N
O
1’
H
H
2’
H
H
nucleotide
O
A nucleotide is the
chemical combination H
N
of base, sugar and
phosphate.
O
N
O
5’
O
O- P O CH2
4’
OH
H
3’
OH
O
1’
H
H
2’
H
H 3C
H
5’
O
The backbone of a
OH
O
nucleic acid 4’is created1’
by connecting
H the
HH
N
H
phosphate of H
this
2’
3’
monomer to the 3’ H
OH
O
N
position of O
5’
O
another O- P O CH2
O
1’
4’
monomer’s OH
scaffolding sugar. H H
H
2’
3’
“From 5’C to 3’C”
H
OH
H3C
H
Nucleotides 3’C
are added
5’C
in the 5’ to
3’ direction
DNA in
3-D
Phosphate connectors,
Right-hand strand 3’ to 5’
Phosphate connectors,
Left-hand strand 5’ to 3’
Scaffolding Sugar & Base
“nucleoside”
End of the Structure of
Nucleic Acids and DNA
Beginning of DNA Replication
DNA: genes on
chromosomes
5’
3’
The DNA strand opens
and will add nucleotides.
G to C and T to A.
One strand grows
continuously, the other
grows discontinuously.
Enzymes join the strands.
3’ 5’
3’ 5’
DNA Replication (inside the nucleus)
“Parental” DNA
DNA Helicase
“Parental” DNA with
a replication fork
DNA
Polymerase
End of DNA Replication
Beginning of RNA Replication
(Transcription)
DNA produces Protein in two steps
Transcription: mRNA production
Translation:
protein production
Transcription of mRNA from DNA
“Parental” DNA
RNA Polymerase
Transcription ~
mRNA Synthesis
Single stranded mRNA
DNA coding sequence
DNA
RNA coding sequence
RNA
INITATION of Transcription
GENE
INITATION of Transcription
Elongation Phase
INITATION of Transcription
Termination Phase
INITATION of Transcription
Multiple mRNA Copies
During Transcription mRNA
code is produced from DNA.
GGG CCC TTT AAA
CCC GGG AAA UUU
To decode DNA
into
these base
What
areRNA
theuse
base
combinations
A-U, T-A, G-C, C-G
code combinations?
Decode the DNA sequence below into mRNA
ATA TAT GCG GCC GAG TCA TAA
UAU AUA CGC CGG CUC AGU AUU
rRNA ~ Ribosomal RNA
Eukaryotic
Ribosome
5,080 RNA base
(in 2 or 3 molecules)
~ 49 embedded proteins
1,900 RNA base
(in a single molecule)
~ 33 embedded proteins
tRNA ~ Transfer RNA
Anticodon mRNA
Binding Site
Amino Acid
Accepting End
End of mRNA Transcription
Beginning of Protein Synthesis
(Translation)
DNA produces Protein in two steps
Transcription: mRNA production
Translation:
protein production
From DNA to RNA to Protein
DNA coding sequence
A- Inside
thesequence
nucleus
RNA
coding
mRNA
B- In the Cytosol
C- At to Ribosome
Base Triplets form the Genetic Code
The “code words” in DNA and RNA are
composed of three contiguous nucleotide
bases called a triplets or CODONs.
Original DNA
GACGACGACGACGAC
Base Sequence
GUCGUCGUCGUCGUC
Translated mRNA
Base Sequence
Remember! RNA
substitutes U for T
The DNA triplets which determine the
mRNA codons ... code for amino acids
at the ribosome... during translation.
tRNA with
and amino
acid in “tow”
tRNA’s... have an “anti-codon”... that
matches the mRNA’s “codon”.
Each of the 20 essential amino acidsmRNA
has it’s own special tRNA’s carriers.
tRNA
mRNA
Translation At the ribosome... an mRNA
mRNA arrives...and tRNA’s begin to
tRNA bring their amino acids... tRNA
Protein anti-codons match up with
mRNA codons... bonds form
between the amino acids.
UUU AAA CCC GGG CCC GGG AUU
AAA UUU GGG CCC GGG CCC UAA
The tRNA’s disengage …
|
|
|
|
|
|
|
Phe Lys Pro Gly Pro Gly Ile
… and the result is a “preprotein” polypeptide chain.
Video
End of Protein Synthesis
(Translation)
Beginning of Extra Slides
concerning DNA and RNA
How is RNA different than DNA?
•Ribose Sugar
•Uracil for
Thymine
•Single strand
•not self
replicating
•found all
over the cell
• Nucleolus - Site of ribosome production
• Nucleus - location of DNA, cell organizer
• Chromosomes - coiled chromatin
• Chromatin - DNA and proteins not coiled
• DNA - helix shaped molecule with base
sequences that make up the genetic code
• RNA - made by DNA, assists DNA to make
proteins as a messenger (mRNA), transfer
molecule (tRNA) and ribosomal RNA
(rRNA).
major groove
minor groove
DNA
DNA
protein
differences between DNA and RNA
DNA
RNA
• deoxyribonucleic acid
• no hydroxyl on 2’ sugar
• ribonucleic acid
• hydroxyl on 2’ sugar
• A, C, G, T
• thymine has methyl group (CH3)
• A, C, G, U
• uracil has a hydrogen atom at position 5
• double stranded
• single stranded or double stranded
• synthesized in 5’ -> 3’ direction
• synthesized in 5’ -> 3’ direction
Information content of various organisms
Organism
Millions of bp (base pairs) of DNA
Human (Homo sapiens)
3000
Yeast (Saccharomyces cerevisiae)
12
Protist (Amoeba dubia)
600000
Bacterium (Mycoplasma genetalium)
0.5
other biological uses for nucleotides/nucleosides
Intracellular communication:
• cyclic adenosine monophosphate (cAMP) is a common chemical
signalling molecule. Caffeine interferes with cAMP signalling
• guanosine triphosphate (GTP) and guanosine diphosphate (GDP) are used
by a class of signalling proteins in the cell. The on/off switch is determined by
what molecule is bound
Energy:
• adenosine triphosphate (ATP) is the energy currency of the cell
• energy is stored in the covalent bonds which link the three phosphates
NH2
N
NH2 O
N
H
N
N
H
N
N
CH2O
OH
O
P
O
N
H
N
NH2
O
O
caffeine
• mimics the effect
of cAMP
• a nucleoside triphosphate is the used to build up the polymer
• two phosphates are liberated (pyrophosphate) when the next nucleotide is added
• this chemical reaction is energetically favorable
ATP
(adenosine triphosphate)
remember, for DNA, dATP is used
ATP is also the energy molecule of the cell