Transcript chapt 8

Chapter 8
Lecture Outline
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8-1
DNA and the Importance
of Proteins
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Proteins play a crucial role in the life of a cell.
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Microtubules, intermediate filaments and
microfilaments maintain the shape of the cell.
Enzymes catalyze important reactions.
The recipes for proteins are found in the
cell’s DNA.
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DNA is organized into genes.
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Each gene is a recipe for a different protein.
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Nucleic Acid Structure
and Function
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DNA accomplishes two things:
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Passes genetic information to the next generation
Controls the synthesis of proteins
DNA is able to accomplish these things
because of its unique structure.
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DNA Structure
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DNA is a nucleic acid.
Nucleic acids
– Large polymers made of
nucleotides
 A sugar molecule
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Deoxyribose for DNA
Ribose for RNA
A phosphate group
A nitrogenous base
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Adenine
– Guanine
– Cytosine
– Thymine
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DNA Structure
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DNA is doublestranded.
– Held together by
hydrogen bonds
between the bases
– A-T, G-C
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Base Pairing Aids DNA Replication
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DNA replication
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Is the process by which DNA is copied
 This is done before cell division.
 Provides the new cells with a copy of
the genetic information
Relies on the base-pairing rules
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Base Pairing Aids DNA
Replication
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Is accomplished by DNA polymerase and other
enzymes
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Helicase binds to DNA and forms a replication bubble by
separating the two strands.
DNA polymerase builds new DNA strands that will pair
with each old DNA strand.
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Where there is an A on the old strand, polymerase will
add a T to the new strand.
When DNA polymerase finishes a segment of new DNA,
it checks its work and corrects mistakes if they happen.
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DNA Replication
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Repairing Genetic Information
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If a mistake is made
when building the new
strand
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The old strand still has
the correct information.
This information can be
used to correct the new
strand.
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The DNA Code
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The order of bases in the DNA molecules is the
genetic information that codes for proteins.
– The sequence of nucleotides forms words that are
like a recipe for proteins.
Each word contains three base letters.
– ATGC are the four letters that are used to make
the words.
– Each three-letter word codes for a specific amino
acid.
The order of amino acids in the protein is determined
by the order of nucleotides in DNA.
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RNA Structure and Function
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RNA vs. DNA
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RNA has ribose sugar
(DNA has deoxyribose).
RNA contains the bases
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Adenine
Guanine
Cytosine
Uracil (DNA has
thymine)
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DNA vs. RNA
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RNA’s, like DNA’s, base sequence carries information.
RNA is made in the nucleus and transported to the
cytoplasm (DNA stays in the nucleus).
The protein coding information in RNA comes from DNA.
Like DNA replication, RNA synthesis follows the basepairing rules (A-U; G-C).
RNA is typically single-stranded (DNA is typically doublestranded).
Three types of RNA participate in protein synthesis
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mRNA
tRNA
rRNA
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Protein Synthesis
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The sequence of nucleotides in a gene dictates
the order of amino acids in a protein.
Before a protein can be made
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The information in DNA must be copied into RNA.
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This process is called transcription.
The information in the RNA can then be used to
make the protein.
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This process is called translation.
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Transcription
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During transcription
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DNA is used as a template to make RNA
Accomplished by RNA polymerase and follows the
base-pairing rules
The process of transcription
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Occurs in the nucleus
RNA polymerase separates the two strands of DNA.
Only one of the two strands will be used to create
the RNA.
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The coding strand
The other DNA strand is called the non-coding strand.
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Transcription of an RNA Molecule
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The Process of Transcription
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Only a segment of the DNA strand will be used to create
each RNA.
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These segments are called genes.
Each gene starts with a promoter.
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Each gene ends with a terminator sequence.
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The RNA polymerase binds to the promoter to start building an
RNA strand.
The RNA polymerase will stop transcribing at the terminator
sequence.
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Translation
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Three types of RNA participate in translation.
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Codons are sets of three nucleotides that
code for specific amino acids.
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mRNA carries the recipe for making the protein.
tRNA and rRNA are used to read the recipe and
build the amino acid chain.
tRNA reads the codons and brings the correct
amino acids.
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The Genetic Code
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Translation
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Ribosomes are organelles that build proteins.
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rRNA is found in ribosomes.
mRNA is read on ribosomes.
Ribosomes are found in two places in the cell.
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Free-floating in the cytoplasm
Bound to the endoplasmic reticulum
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Translation Initiation
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Translation begins when
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The small ribosomal subunit binds to the beginning of the
mRNA and searches for the AUG start codon.
At this point, a tRNA brings the first amino acid.
 The anticodon in the tRNA matches with a codon on the
mRNA.
 Each tRNA carries a specific amino acid based on its
anticodon.
 The start codon, AUG, binds to a tRNA that carries a
methionine.
Finally, the large ribosomal subunit joins the complex and
the next step, translation elongation, can proceed.
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Initiation
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Translation Elongation
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The next tRNA binds with the next codon on the
mRNA.
The ribosome adds this amino acid to the growing
polypeptide.
The ribosome then moves down to the next codon.
The process repeats itself. For each step, a new
amino acid is added to the growing protein.
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Elongation
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Translation Termination
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Elongation continues until the ribosome
encounters a stop codon.
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A release factor binds to the stop codon.
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UAA, UAG, UGA are stop codons.
This causes the ribosome to release the
polypeptide.
The ribosomal subunits separate and release the
mRNA.
The mRNA can be translated again by another
ribosome.
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Termination
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Summary of Protein Synthesis
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The Genetic Code is Nearly
Universal
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The process of making proteins from the
information in DNA is used by nearly all cells.
Nearly all organisms studied to date use the
same genetic code.
Because of this, we are able to use bacteria
as factories to make massive amounts of
proteins.
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Insulin, growth factor, etc.
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Control of Protein Synthesis
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Gene expression is how the cell makes a
protein from the information in a gene.
Cell types are different from one another
because they express different sets of genes.
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Cells control gene expression in response to
different environmental conditions.
Cells can alter gene expression
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Therefore, have different sets of proteins
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Controls the quantity of a protein
Controls the amino acid sequence of a protein
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Control of Protein Quantity
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Cells can regulate how much of a given
protein is made by
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Controlling how much mRNA is available for
translation
Cells do this in a number of ways:
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Regulating how tightly the chromatin is coiled in a
certain region
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The more tightly the chromatin is coiled, the less likely a
gene in that region will be transcribed.
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Eukaryotic Genome Packaging
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Control of Protein Quantity
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By increasing or decreasing the rate of
transcription of the gene by enhancer and silencer
regions on the DNA
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Through the binding of transcription factors,
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These proteins bind to the promoter and facilitate RNA
polymerase binding and transcription.
By limiting the amount of time the mRNA exists in
the cytoplasm,
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Activation of enhancer regions increases transcription.
Activation of silencer regions decreases transcription.
Some mRNA molecules are more stable and will exist
longer in the cytoplasm, yielding more protein.
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Different Proteins from One Gene
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Eukaryotic cells can use one gene to make
more than one protein.
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After transcription, the introns must be cut out
and the coding regions, called exons, must be
put back together.
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In eukaryotic genes, non-coding sequences called
introns, are scattered throughout the sequence.
This is called splicing.
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Transcription of mRNA
in Eukaryotic Cells
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Alternative Splicing
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Different combinations of exons from a single gene
can be joined to build a number of different mRNAs
for a number of different proteins.
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Mutations and Protein Synthesis
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A mutation is any change in the DNA
sequence of an organism.
Can be caused by mistakes in DNA
replication
Can be caused by external factors
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Carcinogens, radiation, drugs, viral infections
Only mutations in coding regions of gene will
change the proteins themselves.
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Point Mutations ̶ a Change in a Single
Nucleotide of the DNA Sequence
Three types:
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A nonsense mutation changes a codon to a stop codon.
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A missense mutation causes a change in the type of amino acid
added to a polypeptide.
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This may change the way in which a protein functions.
UUU (Phe) to GUU (Val)
A silent mutation does not cause a change in the amino acid
sequence.
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This causes the ribosome to stop translation prematurely.
CAA (Gln) to UAA (stop)
UUU to UUC; both code for Phe
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Point Mutations
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Sickle Cell Anemia
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Results from a missense mutation in the gene for
hemoglobin
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GAA to GUA
Glutamic acid to valine change
Causes the hemoglobin protein to change shape
The molecules stick together in low oxygen conditions.
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Get stuck in blood vessels, causing the vessels to break apart easily,
leading to anemia
Also causes blood vessels to clog, preventing oxygen delivery to
tissues, which results in tissue damage
Causes weakness, brain damage, painful joints, etc.
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Normal and Sickled
Red Blood Cells
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Insertions and Deletions
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An insertion mutation occurs when one or
more nucleotides is added to the normal
DNA sequence.
A deletion mutation occurs when one or more
nucleotides is removed from the normal DNA
sequence.
Insertions and deletions cause a frameshift.
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Ribosomes will read the wrong set of three
nucleotides.
Changes the amino acid sequence dramatically
Changes the function of the protein dramatically
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Frameshift
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Mutations Caused by Viruses
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Viruses can insert their genetic material into the DNA
of the host cell.
The presence of the viral material may interfere with
the host cell’s ability to use the genetic material in
that area because of this insertion.
Insertion of human papillomavirus (HPV) causes an
increased risk of cancer.
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Chromosomal Aberrations
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Involves a major change in DNA at the level of the
chromosome
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Inversions occur when a chromosome breaks, and the
broken piece becomes reattached in the wrong orientation.
A translocation occurs when the broken segment becomes
integrated into a different chromosome.
A duplication occurs when a segment of a chromosome is
replicated and attached to the original segment in
sequence.
A deletion occurs when a broken piece is lost or destroyed.
All of these effect many genes, thus many proteins.
In humans, these mutations may cause problems with
fetal development.
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