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• Information flows from DNA to RNA to PROTEIN

The Central Teaching of Molecular Biology

DNA

RNA

PROTEINTranscription

Translation

Blue Print

Construction

1- DNA

2- Synthesis of mRNA in the nucleus 3- mRNA

NucleusCytoplasm

1-DNA

3- mRNA

2- Synthesis of mRNA in the nucleus

Transcription

Cytoplasm

mRNA4- Movement of mRNA into cytoplasm via nuclear pore

Nucleus

Ribosome

4- Movement of mRNA into cytoplasm via nuclear pore

5- Synthesis of Protein5- Synthesis of Protein

6- Polypeptide6- PolypeptideTranslation

• 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.

The Genetic Code & Nucleic Acids

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.

Historical Moments in the Discovery of Nucleic Structure

The four nitrogenous bases in DNA are

NN

N N

H

H

NH2

H

NN

N NH

H

O

NH2

H

N

N

O

H

H3C

H

O

H

N

N

NH2

H

H

H

O

guanine (G)

adenine (A)

cytosine (C)

thymine (T)

Purine bases

Pyrimidinebases

H

                                        

What conclusions could you make from Chargaff’s Data?

A T

C G

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.

Historical Moments in the Discovery of Nucleic Structure

alpha-helix

HydrogenBonds

Polypeptide

Protein

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.

Historical Moments in the Discovery of Nucleic Structure

CenterVertical

Axis

Paired Bases

TwinScaffolding

SugarSpirals

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.

Historical Moments in the Discovery of Nucleic Structure

• 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

Watson & Crick’s DNA Model

End of Introduction to the Central Dogma of Biology

Beginning of the Structure of Nucleic Acids and DNA

•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

T

Ds

Nucleic Acids are Polymers

P

U

RsP

DNA monomer RNA monomer

• Monomeric units are made up of an information carrying nitrogen Base

ScaffoldConnector

Ds

Rs

Base

P

• a sugar Scaffold to hold the base

• a phosphate Connector

Nucleic Acids are Polymers

• Nucleic acids (DNA and RNA) are composed of 4 different nitrogenous bases

NN

N N

H

H

NH2

H

NN

N N

H

H

O

NH2

H

N

N

O

H

H3C

H

O

H

N

N

NH2

H

H

H

OG

A

C

T

purines pyrimidines

NN

N N

H

H

NH2

H

NN

N N

H

H

O

NH2

H

N

N

O

H

H3C

H

O

H

N

N

NH2

H

H

H

OG

A

C

T

•Each have H bond donors and acceptors

purines pyrimidines

NN

N N

H

H

NH2

H

NN

N N

H

H

O

NH2

H

N

N

O

H

H3C

H

O

H

N

N

NH2

H

H

H

OG

A

C

T

•A-T base pairs form 2 H bonds & G-C base pairs form 3 H bonds

purines pyrimidines

• In RNA the base Thymine (T) is replaced by Uracil (U)

NN

N N

H

H

NH2

H

NN

N N

H

H

O

NH2

HN

N

NH2

H

H

H

OC

T

G

A

purines pyrimidines

U

In RNA the scaffold is ribose, a pentose (five carbon) sugar

H H

OH OH

OH

H

OHCH2

H

O

1’

2’

4’

H H

OH H

OH

H

OHCH2

H

O

1’

2’

4’

In DNA the scaffold is 2’-deoxyribose, a pentose (five carbon) sugar

3’3’

5’ 5’

In both DNA and RNA the base is connected to the 1’ position of the scaffolding sugar *

H H

OH H

OH

HH

O

1’

2’

4’

N

N

O

H

H3C

H

O

H

OHCH2

* (liberating water - dehydration synthesis)

5’

3’

P

In both DNA and RNA a phosphate connector is added to the 5’ position of the scaffolding sugar

H H

OH H

O

H

OHCH2

H

O

1’

2’

4’

N

N

O

H

H3C

O

H

O-

O- O

O

3’

5’

P

A nucleoside is the chemical combination of base and sugar.

H H

OH H

O

H

CH2

H

O

1’

2’

4’

N

N

O

H

H3C

O

H

O- O

O

O-

nucleoside

5’

3’

P

A nucleotide is the chemical combination of base, sugar and phosphate.

H H

OH H

O

H

CH2

H

O

1’

2’

4’

N

N

O

H

H3C

O

H

O- O

O

O-

nucleotide

5’

3’

P

The backbone of a nucleic acid is created by connecting the phosphate of this monomer to the 3’ position of another monomer’s scaffolding sugar. H H

OH H

O

H

CH2

H

O

1’

2’

4’

5’

N

N

O

H

H3C

O

H

O- O

O

O-

H H

OH H

OH

HH

O

1’

2’3’

4’

5’

“From 5’C to 3’C”3’

5’C

3’CNucleotides are added in the 5’ to 3’ direction

Phosphate connectors, Right-hand strand 3’ to 5’

Scaffolding Sugar & Base“nucleoside”

Phosphate connectors, Left-hand strand 5’ to 3’

3-D3-DDNA in

End of the Structure of Nucleic Acids and DNA

Beginning of DNA Replication

DNA: genes on chromosomes

The DNA strand opens and will add nucleotides. G to C and T to A.

5’ 3’

5’3’

One strand grows continuously, the other grows discontinuously.

Enzymes join the strands.5’ 3’

DNA Replication (inside the nucleus)

“Parental” DNA

“Parental” DNA with a replication fork

DNA Helicase

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

Transcription ~ mRNA Synthesis

RNA Polymerase

Single stranded mRNA

RNA

DNADNA coding sequence

RNA coding sequence

GENE

INITATION of Transcription

Elongation Phase

INITATION of Transcription

Termination Phase

INITATION of Transcription

Multiple mRNA Copies

INITATION of Transcription

During Transcription mRNA code is produced from DNA.

GGG CCC TTT AAA

CCC GGG AAA UUU

To decode DNA into RNA use these base combinations A-U, T-A, G-C, C-G

Decode the DNA sequence below into mRNA ATA TAT GCG GCC GAG TCA TAA

UAU AUA CGC CGG CUC AGU AUU

What are the base code combinations?

~ Ribosomal RNA

5,080 RNA base(in 2 or 3 molecules)~ 49 embedded proteins

1,900 RNA base(in a single molecule)~ 33 embedded proteins

Eukaryotic Ribosome

rRNA

~ Transfer RNA

Anticodon mRNA Binding Site

tRNA

Amino Acid Accepting End

Beginning of Protein Synthesis(Translation)

End of mRNA Transcription

DNA produces Protein in two steps

Transcription: mRNA production

Translation: protein production

From DNA to RNA to ProteinDNA coding sequence

RNA coding sequenceA- Inside the nucleus

C- At to Ribosome

B- In the Cytosol

mRNA

GUCGUCGUCGUCGUC

Base Triplets form the Genetic Code

Original DNABase Sequence

GACGACGACGACGAC

Triplets

The “code words” in DNA and RNA are composed of three contiguous nucleotide

bases called a triplets or CODONs.

Translated mRNABase 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... that matches the mRNA’s “codon”.

have an “anti-codon”...

Each of the 20 essential amino acids has it’s own special tRNA’s carriers.

mRNA

tRNA

mRNA

AAA|

Phe

UUU|

Lys

GGG|

Pro

CCC|

Gly

GGG|

Pro

CCC|

Gly

UAA|

Ile

At the ribosome... an mRNA arrives... and tRNA’s begin to bring their amino acids... tRNA anti-codons match up with mRNA codons...

The tRNA’s disengage …

… and the result is a “pre-protein” polypeptide chain.

UUU AAA CCC GGG CCC GGG AUU

bonds form between the amino acids.

Translation mRNA tRNA Protein

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 • ribonucleic acid• no hydroxyl on 2’ sugar • hydroxyl on 2’ sugar

• A, C, G, T • A, C, G, U• thymine has methyl group (CH3) • 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

N N

N N

CH2O

H

NH2

H

OHP

O

O O

N N

N N

H

NH2

O

NH2

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 usedATP is also the energy molecule of the cell

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