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DNA structure Remember Ch 3 we learned the building block to the macromolecules of life Question What are the building blocks of nucleic acids? Copyright © 2009 Pearson Education, Inc.
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DNA structure Remember Ch 3 we learned the building blocks to the macromolecules of life Question What are the building blocks of nucleic acids? Nucleotides! Copyright © 2009 Pearson Education, Inc.
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10.2 DNA and RNA are polymers of nucleotides
The monomer unit of DNA and RNA is the nucleotide, containing Nitrogenous base 5-carbon sugar Phosphate group Copyright © 2009 Pearson Education, Inc.
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10.2 DNA and RNA are polymers of nucleotides
The monomer unit of DNA and RNA is the nucleotide, containing Nitrogenous base 5-carbon sugar Phosphate group Copyright © 2009 Pearson Education, Inc.
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10.3 DNA is a double-stranded helix
James D. Watson and Francis Crick deduced the secondary structure of DNA, with X-ray crystallography data from Rosalind Franklin and Maurice Wilkins Specific pairs of bases give the helix a uniform shape A pairs with T, forming two hydrogen bonds G pairs with C, forming three hydrogen bonds The specific nature of the base-pairing interactions not only accounted for the uniform diameter of the double helix but also conformed to the chemical characteristics of the nucleotide bases and chemical composition studies of DNA. RNA molecules have secondary structure that involves hydrogen bonding between bases on the same polynucleotide chain. Thus the structure will be unique to RNA of a specific sequence. The covalent bonding between nucleotides can be contrasted with the hydrogen bonding between bases. Although individual hydrogen bonds are weaker than covalent bonds, the large number of hydrogen bonds along a double helical DNA molecule stabilizes the helix. Hydrogen bonds can be temporarily disrupted so that the DNA strands separate, but each individual strand remains intact. Copyright © 2009 Pearson Education, Inc.
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Watson and Crick in 1953 with their model of the DNA double helix
Watson and Crick in 1953 with their model of the DNA double helix Figure 10.3B Watson and Crick in 1953 with their model of the DNA double helix.
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3-D structure of DNA Licorice Toothpicks Marshmallows Phosphate group
Licorice Phosphate group Toothpicks 5-carbon sugar Marshmallows Nitrogenous bases Green = Adenine Yellow =Guanine Pink = Thymine Orange = Cytosine Create both sides of DNA strand
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Replication of DNA is a zipping action
Create both sides of DNA strand
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DNA replication follows a semiconservative model
DNA replication follows a semiconservative model Parental molecule of DNA Figure 10.4A A template model for DNA replication. This figure emphasizes the accuracy of DNA replication, due to the specific base-pairing interactions. When the strand on the left is a template, the complementary strand is identical to the one on the right and vice versa.
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The two DNA strands separate
Each strand is used as a pattern to produce a complementary strand, using specific base pairing Nucleotides Parental molecule of DNA Both parental strands serve as templates Figure 10.4A A template model for DNA replication. This figure emphasizes the accuracy of DNA replication, due to the specific base-pairing interactions. When the strand on the left is a template, the complementary strand is identical to the one on the right and vice versa.
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Each new DNA helix has one old strand with one new strand
Each new DNA helix has one old strand with one new strand Nucleotides Parental molecule of DNA Both parental strands serve as templates Two identical daughter molecules of DNA Replicate licorice model
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Two daughter DNA molecules
Parental strand Origin of replication Daughter strand Bubble DNA replication occurs in many sections simultaneously Two daughter DNA molecules
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Overall direction of replication
DNA polymerase molecule 3 5 Daughter strand synthesized continuously Parental DNA 5 3 Daughter strand synthesized in pieces 3 5 5 Figure 10.5C How daughter DNA strands are synthesized. Continuous synthesis and discontinuous synthesis are depicted in this figure. DNA synthesis beginning on the template oriented in the 3′ 5′ direction can continue as the unwinding of the replication fork provides additional template in the direction of synthesis. Enzymes synthesizing DNA on the template oriented in the 5′ 3′ direction are moving away from the replication fork, so short discontinuous fragments are produced. As more of the template strand is unwound, an enzyme can bind and synthesize the complementary strand. These short Okasaki fragments are joined by DNA ligase to form a continuous nucleotide chain. 3 DNA ligase Overall direction of replication
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Now we know how to get more DNA
Where do RNA and proteins come into play? Novelty Gene Copyright © 2009 Pearson Education, Inc.
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THE FLOW OF GENETIC INFORMATION FROM DNA TO RNA TO PROTEIN
Copyright © 2009 Pearson Education, Inc.
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From Gene to Protein What is a gene? What is a protein?
Give some examples of genes. What is a protein? Give some examples of proteins.
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From Gene to Protein Most of us have a protein enzyme that can synthesize melanin the main pigment that gives color to our skin and hair Albino people make a defective version of this protein enzyme They are unable to make melanin and they have very pale skin and hair
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From Gene to Protein The instructions for making a protein are provided by a gene, which is a specific segment of a DNA molecule. Each gene contains a specific sequence of nucleotides. This sequence of nucleotides specifies which sequence of amino acids should be joined together to form the protein. The sequence of amino acids in the protein determines the structure and function of the protein. For example, the defective enzyme in albinos has a different amino acid sequence than the normal enzyme for synthesizing melanin.
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From Gene to Protein A gene directs the synthesis of a protein by a two-step process. Transcription-DNA is copied into a messenger RNA (mRNA) molecule. The sequence of nucleotides in the gene determines the sequence of nucleotides in the mRNA. Translation - mRNA is used by ribosomes to insert the correct amino acids in the correct sequence to form the protein coded for by that gene. The sequence of nucleotides in the mRNA determines the sequence of amino acids in the protein.
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From Gene to Protein The following table summarizes the basic characteristics of transcription and translation. Original message or instructions in: Molecule which is synthesized Location where this takes place Transcription Nucleotide sequence in gene in DNA in chromosome Nucleus Translation
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From Gene to Protein The following table summarizes the basic characteristics of transcription and translation. Original message or instructions in: Molecule which is synthesized Location where this takes place Transcription Nucleotide sequence in gene in DNA in chromosome mRNA Nucleus Translation Nucleotide sequence in mRNA Protein Cytoplasm/ribosomes
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Synthesis of Hemoglobin
What is hemoglobin? We will begin with the process of transcription to make hemoglobin. Remember, transcription is the process that makes messenger RNA (mRNA) RNA is different from DNA in that it is single stranded and has the 5-carbon sugar ribose is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates,[1] and the tissues of some invertebrates. Hemoglobin transports oxygen from the lungs or gills to the rest of the body where it releases the oxygen for cell use
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RNA polymerase separates the two DNA strands and elongates the mRNA
When the mRNA is synthesized, RNA nucleotides are added one at a time by RNA polymerase, and each RNA nucleotide is matched to the corresponding DNA nucleotide in the gene. The base-pairing rule is very similar to the base-pairing rule in the DNA double helix, but what is the one difference? Complementary nucleotides for base-pairing between two strands of DNA for base-pairing between DNA and RNA G (guanine) pairs with C (cytosine). G pairs with C. A (adenine) pairs with T (thymine). A in DNA pairs with U (uracil) in RNA. T in DNA pairs with A in RNA. is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates,[1] and the tissues of some invertebrates. Hemoglobin transports oxygen from the lungs or gills to the rest of the body where it releases the oxygen for cell use
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RNA polymerase separates the two DNA strands and elongates the mRNA
is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates,[1] and the tissues of some invertebrates. Hemoglobin transports oxygen from the lungs or gills to the rest of the body where it releases the oxygen for cell use RNA polymerase can add up to 50 nucleotides per second
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Transcription modeling
DNA nucleotide Complementary nucleotide in RNA G C T A
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Transcription modeling
Notice that the process of transcription is similar to the process of DNA replication. What are some similarities between transcription and DNA replication? What are some of the differences? DNA replication Transcription The whole chromosome is replicated. ___________________is transcribed. DNA is made. DNA is double-stranded. mRNA is made. mRNA is _____________ -stranded. DNA polymerase is the enzyme which carries out DNA replication. _____ polymerase is the enzyme which carries out transcription. T = thymine is used in DNA, so A pairs with T in DNA. T = thymine is replaced by ___ = uracil in RNA, so A in DNA pairs with ___ in mRNA.
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Summary To summarize what you have learned, explain how a gene directs the synthesis of an mRNA molecule. Include in your explanation the words and phrases: base-pairing rule, complementary nucleotides, cytoplasm, DNA, gene, messenger RNA, nucleotide, nucleus, and RNA polymerase.
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Translation In the process of translation, the sequence of nucleotides in messenger RNA (mRNA) determines the sequence of amino acids in a protein. The figure below shows an example of how transcription is followed by translation.
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Translation Codon – In translation, three nucleotides in an mRNA molecule codes for one amino acid in a protein Each codon specifies a particular amino acid. For example, the first codon shown, CGU, instructs the ribosome to put the amino acid arg (arginine) as the first amino acid in this protein. mRNA codon Amino acid ACU Threonine (Thr) CAU Histidine (His) CCU Proline (Pro) CUG Leucine (Leu) GAG Glutamic acid (Glu) GUG Valine (Val)
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10.8 The genetic code is the Rosetta stone of life
Redundant: More than one codon for some amino acids Unambiguous: Any codon for one amino acid does not code for any other amino acid Nearly universal Exceptions to the universality of the genetic code are found for both mitochondrial and nuclear genes. In mitochondria from animals and microorganisms such as yeast, UGA codes for tryptophan rather than stop. In vertebrate mitochondria, AGA and AGG are stop codons instead of specifying arginine. In yeast mitochondria, all codons beginning with CU code for threonine instead of leucine, while the codons UUA and UUG still specify leucine. For the nuclear genes of the ciliated protozoan Tetrahymena thermophila, UAA and UAG code for glutamine rather than stop. Copyright © 2009 Pearson Education, Inc.
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Second base First base Third base
First base Third base Figure 10.8A Dictionary of the genetic code (RNA codons). This listing of the codon “dictionary” can be used to illustrate the triplet and redundant nature of the code. While methionine and tryptophan have only one codon each, leucine, serine, and arginine each have six codons. It can also be pointed out that codons for the same amino acid often differ in the third nucleotide, a phenomenon described as “wobble.” The base pairing of the first two nucleotides of the codon with corresponding positions in the anticodon is stringent, but pairing of the third is weaker and more flexible. The wobble hypothesis proposed by Francis Crick allows for some nonstandard pairings that account for some of the redundancy of the genetic code. For example, if the third position of the codon is a U or C, it can pair with a G on the anticodon. This would mean that one tRNA, rather than two, could be used to translate UUU and UUC, for example. Estimates of 30–50 tRNAs necessary to pair with 61 codons are borne out by studies that identify 45 different tRNAs in some cell types.
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How does translation actually take place?
Transfer RNA (tRNA) molecules match an amino acid to its corresponding mRNA codon tRNA structure allows it to convert one language to the other (the nucleic acid language to protein language) An amino acid attachment site allows each tRNA to carry a specific amino acid An anticodon on tRNA allows the tRNA to bind to a specific mRNA codon, complementary in sequence A pairs with U, G pairs with C
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How does translation actually take place?
There are multiple different types of tRNA. Each type of tRNA molecule can bind to one specific type of amino acid on one end. On the other end, the tRNA molecule has three nucleotides that form an anti-codon. The three nucleotides in the tRNA anti-codon are complementary to the three nucleotides in the mRNA codon for that specific type of amino acid.
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How does translation actually take place?
Where are the anticodons and codons in this picture?
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How does translation actually take place?
Amino acid mRNA codon Anti-codon in tRNA molecule that carries this amino acid Threonine (Thr) ACU UGA Histidine (His) CAU Proline (Pro) CCU Leucine (Leu) CUG Glutamic acid (Glu) GAG Valine (Val) GUG
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How does translation actually take place?
Amino acid mRNA codon Anti-codon in tRNA molecule that carries this amino acid Threonine (Thr) ACU UGA Histidine (His) CAU GUA Proline (Pro) CCU GGA Leucine (Leu) CUG GAC Glutamic acid (Glu) GAG CUC Valine (Val) GUG CAC
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Translation occurs on a ribosome
Copyright © 2009 Pearson Education, Inc.
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Next amino acid to be added to Polypeptide- A site Growing Polypeptide
Next amino acid to be added to Polypeptide- A site Growing Polypeptide - P site tRNA mRNA Figure 10.12C A ribosome with occupied binding sites. This figure shows that one of the tRNA binding sites (P site) holds the growing peptide chain while the adjacent site (A site) holds the tRNA carrying the next amino acid to be added to the chain. Codons A – site think add site P – site think protein site
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10.13 An initiation codon marks the start of an mRNA message
Initiation brings together the components needed to begin RNA synthesis Initiation occurs in two steps mRNA binds to a small ribosomal subunit, and the first tRNA binds to mRNA at the start codon A large ribosomal subunit joins the small subunit, allowing the ribosome to function The first tRNA occupies the P site, which will hold the growing peptide chain The A site is available to receive the next tRNA Copyright © 2009 Pearson Education, Inc.
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Met Met Large ribosomal subunit Initiator tRNA P site A site Start
Met Met Large ribosomal subunit Initiator tRNA P site A site Start codon mRNA Figure 10.13B The initiation of translation. The two-step process of initiation is shown in this figure. In prokaryotic cells, the binding of the first tRNA, formyl-methionine (f-met) tRNA has been shown to stabilize the initiation complex. Small ribosomal subunit 1 2
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10.14 Elongation adds amino acids to the polypeptide chain until a stop codon terminates translation
Elongation is the addition of amino acids to the polypeptide chain Each cycle of elongation has three steps Codon recognition: next tRNA binds to the mRNA at the A site Peptide bond formation: joining of the new amino acid to the chain Amino acids on the tRNA at the P site are attached by a covalent bond to the amino acid on the tRNA at the A site Peptide bond formation represents another dehydration synthesis reaction. It is catalyzed by the enzyme peptidyl transferase. Translocation has also been described as a movement of the ribosome. Since the tRNA/mRNA hydrogen bonding remains intact, a shift of the ribosome would cause the tRNA in the A site to occupy the P site. There is also an E site, to the left of the P site. When the ribosome shifts positions, the tRNA from the P site moves into the E site and then is released to the cytoplasm. Copyright © 2009 Pearson Education, Inc.
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10.14 Elongation adds amino acids to the polypeptide chain until a stop codon terminates translation
Translocation: tRNA is released from the P site and the ribosome moves tRNA from the A site into the P site Elongation continues until the ribosome reaches a stop codon Peptide bond formation represents another dehydration synthesis reaction. It is catalyzed by the enzyme peptidyl transferase. Translocation has also been described as a movement of the ribosome. Since the tRNA/mRNA hydrogen bonding remains intact, a shift of the ribosome would cause the tRNA in the A site to occupy the P site. There is also an E site, to the left of the P site. When the ribosome shifts positions, the tRNA from the P site moves into the E site and then is released to the cytoplasm. Copyright © 2009 Pearson Education, Inc.
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Amino acid Polypeptide P site A site Anticodon mRNA Codons 1 Codon recognition Figure Polypeptide elongation.
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Amino acid Polypeptide P site A site Anticodon mRNA Codons 1 Codon recognition Figure Polypeptide elongation. 2 Peptide bond formation
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Amino acid Polypeptide P site A site Anticodon mRNA Codons 1 Codon recognition Figure Polypeptide elongation. 2 Peptide bond formation New peptide bond 3 Translocation
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Amino acid Polypeptide P site A site Anticodon mRNA Codons 1 Codon recognition mRNA movement Stop codon Figure Polypeptide elongation. 2 Peptide bond formation New peptide bond 3 Translocation
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Modeling Translation Peptide bond formation represents another dehydration synthesis reaction. It is catalyzed by the enzyme peptidyl transferase. Translocation has also been described as a movement of the ribosome. Since the tRNA/mRNA hydrogen bonding remains intact, a shift of the ribosome would cause the tRNA in the A site to occupy the P site. There is also an E site, to the left of the P site. When the ribosome shifts positions, the tRNA from the P site moves into the E site and then is released to the cytoplasm. Copyright © 2009 Pearson Education, Inc.
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Check your comprehension
What is the function of mRNA? What is the function of tRNA? Describe one similarity in the structure of mRNA and tRNA. Describe one difference between the structure of mRNA and tRNA. The proteins in biological organisms include 20 different kinds of amino acids. What is the minimum number of different types of tRNA molecules that must exist in the cell? 41 = ? = ? = ? Explain why it makes sense to use the word translation to describe protein synthesis. Explain why it would not make sense to use the word translation to describe mRNA synthesis. What part of translation depends on the same base-pairing rule that is used in transcription and DNA replication? You have modeled how ribosomes carry out translation. Why is it appropriate to say that the function of ribosomes is protein synthesis? Peptide bond formation represents another dehydration synthesis reaction. It is catalyzed by the enzyme peptidyl transferase. Translocation has also been described as a movement of the ribosome. Since the tRNA/mRNA hydrogen bonding remains intact, a shift of the ribosome would cause the tRNA in the A site to occupy the P site. There is also an E site, to the left of the P site. When the ribosome shifts positions, the tRNA from the P site moves into the E site and then is released to the cytoplasm. Copyright © 2009 Pearson Education, Inc.
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10.16 Mutations can change the meaning of genes
A mutation is a change in the nucleotide sequence of DNA Base substitutions: replacement of one nucleotide with another Effect depends on whether there is an amino acid change that alters the function of the protein Deletions or insertions Alter the reading frame of the mRNA, so that nucleotides are grouped into different codons Lead to significant changes in amino acid sequence downstream of mutation Cause a nonfunctional polypeptide to be produced Copyright © 2009 Pearson Education, Inc.
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10.16 Mutations can change the meaning of genes
Mutations can be Spontaneous: due to errors in DNA replication or recombination Inherited Induced by mutagens High-energy radiation Chemicals Copyright © 2009 Pearson Education, Inc.
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Sickle-cell hemoglobin
Sickle Cell Anemia Normal hemoglobin DNA Mutant hemoglobin DNA mRNA mRNA Figure 10.16A The molecular basis of sickle-cell disease. This figure shows the base pair change that leads to the formation of sickle cell hemoglobin. This results in an amino acid change in the protein, from glutamic acid to valine. This substitution of a hydrophobic amino acid for a hydrophilic one causes a significant difference in the activity of the -hemoglobin chain. Normal hemoglobin molecules exist as individual units whether they are bound to oxygen or not. Sickle cell hemoglobin molecules are also single entities when oxygen is bound, but they form large polymers that distort the shape of the cell when oxygen is released to the tissues. The cells may have an irregular appearance or assume the crescent or sickle shape for which the disease is named. These misshapen cells tend to clog blood vessels, leading to pain, infection, and damage to organs. Cells with sickle cell hemoglobin have a shorter lifetime than normal cells (10–20 days as opposed to 3 months) so anemia sets in because the bone marrow is unable to produce new cells as rapidly as they are removed from the population. This example demonstrates that a seemingly small change, a difference of one base pair leading to a change in a single amino acid (out of 147), can have severe effects. Normal hemoglobin Sickle-cell hemoglobin Glu Val
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Normal gene mRNA Protein Met Lys Phe Gly Ala Base substitution Met Lys
mRNA Protein Met Lys Phe Gly Ala Base substitution Met Lys Phe Ser Ala Figure 10.16B Types of mutations and their effects. This figure contrasts the multiple amino acid changes caused by a deletion with the single amino acid change caused by a substitution. Base deletion Missing Met Lys Leu Ala His
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