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Expression of Genetic Information : FromTranscription to Translation
Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC, FIBADepartment of Pharmacology and Molecular Biology
Faculty of Medicine, Methodist University of Indonesia - Medan
Molecular Biology Research, Postgraduate School,
University of Sumatra Utara - Medan
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The DNA Double Helix
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The Flow of Information in a Eukaryotic Cell
DNA RNA Protein
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The pathway from DNA to Protein
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How is the relationship
between genes and proteins ?
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A Scottish Physician
1908 Archibald Garrot, reported thesymptoms exhibited by persons with certainrare inherited diseases were caused by the
absence of specific enzyme. The disease wasalcaptonuria, because the urine becomesdark on exposure to air.
Garrod found that persons with alcaptonurialacked an enzyme in their blood.
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Lack of homogentisate oxidase in alcaptonuria
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Inborn error of metabolism by Garrod
Relationship between a genetic defect, a specificenzyme, and a specific metabolism condition.
Hypothesis One gene - one enzyme.
One gene - one polypeptide.
Modification
A single gene often generates a variety of
polypeptide.
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The BeadleTatum Experiment in 1940s
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Conclusion of the BeadleTatum Experiment
The cell have an enzymatic deficiency that prevents them
from synthesizing this essential compound (e.g.
panthothenic acid of coenzyme A).
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Genes can be expressed with different efficiencies
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Complementary base pairs in the DNA
double helix
Uracil form base pairs with adenine
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Differences
between DNA
and RNA
1. The nucleotide in
RNA are
ribonucleotides,
containing sugar ribose
(ribonucleic acid)rather than
deoxyribose
2. Like DNA, RNA
contains the basesadenine (A), guanine
(G), and cytosine (C), it
contains the base uracil
(U) instead of thymine
(T) in DNA.
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DNA always occur in cells as a double-strandedhelix, RNA is single-stranded.
RNA chain can fold up into a particular shape, justas a polypeptide chain folds up to form the final
shape of a protein.
The ability of RNA to fold into complex three-
dimensional shapes allows some RNA molecules to
have precise structural and catalytic functions.
Differences between DNA and RNA
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RNA can fold into specific structure
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From DNA to RNA
The RNA in a cell is made by DNA transcription.
Transcription begins with the opening and
unwinding of a small portion of the DNA doublehelix.
One of the two strands of the DNA double helixthen acts as a template for the synthesis of an RNAmolecule.
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From DNA to RNA
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The nucleotide sequence of the RNA chain is
determined by the complementary base-pairing
between incoming nucleotides and the DNA
template.
The RNA chain producedthe transcriptis
therefore elongated one nucleotide at a time. It hasa nucleotide sequence that is exactly
complementary to the strand used as the template.
From DNA to RNA
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Unlike a newly formed DNA, the RNA strand doesnot remain hydrogen-bonded to the DNA templatestrand. Instead, just behind the region whereribonucleotides are being added.
The RNA chain is displaced and the DNA helixreforms.
Because RNA are copied from only a limited regionof the DNA, RNA molecules are much shorter thanDNA molecule.
Differences in DNA and RNA Replication
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Transcription of two genes as observed under
the electrone microscope
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Question
How DNA molecule is copied
into RNA (transcription) inprocaryote and eucaryote ?
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Transcription Process in Procaryote
Require RNA polymerase holoenzyme
Play a role in transcription process :
- Binding of the polymerase to the DNA
template.
- Initiation of transcription.
- Elongation.
- Termination.
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Steps in transcription cycle of bacterial RNA polymerase
1. The RNA polymerase holoenzyme (polymerase coreenzyme plus factor) assembles and locates a promoter.
2. Promoter unwinds the DNA at the position in whichtranscription is to begin.
3. The initial RNA synthesis (aborted initiation) is relativelyinefficient.
4. Once RNA polymerase has managed to synthesize about10 nucleotides of RNA, it breaks its interaction with thepromoter DNA.
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5. During the elongation mode, transcription is
highly processive, with the polymerase leaving the
DNA template and releasing the newly transcribed
RNA only when it encounters a termination signal.
Step 6 & 7. Termination signal are typically
encoded in DNA. Many function by forming an
RNA structure that destabilizes the polymerases
hold on the RNA.
Steps in transcription cycle of bacterial RNA polymerase
h l f b l l
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The transcription cycle of bacterial RNA polymerase
(Procaryote)
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The importance of RNA polymerase orientation
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Transcription Process in Eukaryotes
Require for a large variety of accessoryproteins, or transcription factors.
Play a role in transcription process :- Binding of the polymerase to the DNA
template.
- Initiation of transcription.
- Elongation.
- Termination.
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Transcription Initiation in eucaryotic cell requires many proteins
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Initiation of transription of a
eucaryotic gene by RNA
polymerase
The promoter contains a DNAsequence called the TATA box, located
25 nucleotides away from the sites at
which transcription is initiated.
Through its subunit TBP, TFIIDrecognizes and binds the TATA box.
The RNA polymerase itselfassemble at the promoter.
TFII H uses ATP to pry apart theDNA double helix.
The site of phosphorylation is along C terminal polypeptide tail,
called C terminal domain (CTD).
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Summary of the steps leading from gene to protein in
eucaryote and bacteria (procaryote)
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Control of Gene Expression
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