The central dogma of molecular biology. Bacteriophages attached to the surface of a bacterium. Page 84.
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The central dogma of molecular biology.
Bacteriophages attached to the surface of a bacterium.
Pag
e 84
FIGURE 17.10 The Hershey-Chase Experiment
The Hershey-Chase experiment.
1952 Alfred Hershey and Martha Chase
Diagram of T2 bacteriophage injecting its DNA into an E. coli cell.
FIGURE 17.9 Fred Griffith’s Experiment
WHAT IS DNA?
Scientists have studied how organisms organize and process genetic information, revealing the following principles:
1. DNA directs the function of living cells and is transmitted to offspring
DNA is composed of two polydeoxynucleotide strands forming a double helix
Figure 17.2 Two Models of DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
A gene is a DNA sequence that contains the base sequence information to code for a gene product, protein, or RNAThe complete DNA base sequence of an organism is its genomeDNA synthesis, referred to as replication, involves complementary base pairing between the parental and newly synthesized strand
Figure 17.2 Two Models of DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
2. The synthesis of RNA begins the process of decoding genetic information
RNA synthesis is called transcription and involves complementary base pairing of ribonucleotides to DNA basesEach new RNA is a transcriptThe total RNA transcripts for an organism comprise its transcriptome
Figure 17.3a An Overview of Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
3. Several RNA molecules participate directly in the synthesis of protein, or translation
Messenger RNA (mRNA) specifies the primary protein sequenceTransfer RNA (tRNA) delivers the specific amino acidRibosomal RNA (rRNA) molecules are components of ribosomes
Figure 17.3b An Overview of Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
The proteome is the entire set of proteins synthesized
4. Gene expression is the process by which cells control the timing of gene product synthesis in response to environmental or developmental cues
Metabolome refers to the sum total of low molecular weight metabolites produced by the cell
Figure 17.3b An Overview of Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
The Central dogma schematically summarizes the previous information
Includes replication, transcription, and translationThe central dogma is generally how the flow of information works in all organisms, except some viruses have RNA genomes and use reverse transcriptase to make DNA (e.g., HIV)
Section 17.1: DNA
DNA RNA Protein
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
DNA consists of two polydeoxynucleotide strands that wind around each other to form a right-handed double helix
Each DNA nucleotide monomer is composed of a nitrogenous base, a deoxyribose sugar, and phosphate
Figure 17.4 One strand of DNA
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Nucleotides are linked by 3′,5′-phosphodiester bonds
These join the 3′-hydroxyl of one nucleotide to the 5′-phosphate of another
Figure 17.4 DNA Strand Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
5’
3’
5’
3’
FIGURE 17.11 X-Ray Diffraction Study of DNA by Rosalind Franklin and R. Gosling
Two strands of DNA are oriented in opposite orientations –they are antiparallel.
The antiparallel nature of the two strands allows hydrogen bonds to form between the nitrogenous bases
Two types of base pair (bp) in DNA: (1) adenine (purine) pairs with thymine (pyrimidine) and (2) the purine guanine pairs with the pyrimidine cytosine
Figure 17.5 DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
3’
5’
5’
3’
Oxygen is missing in 2’deoxyribose
Page 40
Page 40
The dimensions of crystalline B-DNA have been precisely measured:
1. One turn of the double helix spans 3.32 nm and consists of 10.3 base pairs
Figure 17.6 DNA Structure: GC Base Pair Dimensions
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
2. Diameter of the double helix is 2.37 nm, only suitable for base pairing a purine with a pyrimidine3. The distance between adjacent base pairs is 0.29-0.30 nm
Figure 17.6 DNA Structure: AT Base Pair Dimensions
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
DNA is a relatively stable molecule with several noncovalent interactions adding to its stability
1. Hydrophobic interactions—internal base clustering2. Hydrogen bonds—formation of preferred bonds: three between CG base pairs and two between AT base pairs3. Base stacking—bases are nearly planar and stacked, allowing for weak van der Waals forces between the rings4. Hydration—water interacts with the structure of DNA to stabilize structure5. Electrostatic interactions—destabilization by negatively charged phosphates of sugar-phosphate backbone are minimized by the shielding effect of water on Mg2+
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Tautomerism of nucleobases• Prototropic tautomers are structural isomers that
differ in the location of protons• Keto-enol tautomerism is common in ketones• Lactam-lactim tautomerism occurs in some
heterocycles• Both tautomers exist in solution but the lactam
forms are predominant at neutral pH
FIGURE 17.7 A Tautomeric Shift Causes a Transition Mutation
DNA Structure: The Nature of MutationDNA Structure: The Nature of MutationDNA is eminently suited for information storage but not staticDespite its stability, it is vulnerable to certain disruptive forces that can cause mutations
Most negative or neutral rare positive mutations can enhance the adaptation of the organism
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Mutation types—The most common are small single base changes, also called point mutations
This results in transition or transversion mutationsTransition mutations, caused by deamination, lead to purine for purine or pyrimidine for pyrimidine substitutionsTransversion mutations, caused by alkylating agents or ionizing radiation, occur when a purine is substituted for a pyrimidine or vice versa
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Point mutations that occur in a population with any frequency are referred to as single nucleotide polymorphisms (SNPs)
Point mutations that occur within the coding portion of a gene can be classified according to their impact on structure and/or function:
Silent mutations have no discernable effectMissense mutations have an observable effectNonsense mutations changes a codon for an amino acid to that of a premature stop codon
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Inversions result when deleted DNA is reinserted into its original position in the opposite orientationTranslocation is when a DNA fragment inserts else where in the genomeDuplication is the creation of duplicate genes or parts of genes.
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Tautomeric shifts are spontaneous changes to nucleotide base structure
Amino to imino groups and keto to enol groupsIf tautomers form during replication, base mispairings can occur
The imino form of adenine does not pair with thymine; it pairs with cytosine
Several spontaneous hydrolytic reactions can cause DNA damage
Depurination or deamination is also possible, which could cause a mutation in the next round of replication
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Figure 17.7 A Tautomeric Shift Causes a Transition Mutation
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Ionizing radiation (e.g., UV and X-rays) can alter DNA structureRadiation-induced damage via free radical mechanisms can cause strand breaks, DNA-protein cross linking, ring openings, and base modificationsThe most common UV-induced products are thymine-thymine dimers
Figure 17.8 Thymine Dimer Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Xenobiotics can damage DNA; classes include:Base analogues have structures so similar to bases they can be incorporated into DNA Alkylating agents cause alkylation, which is the electrophilic attack on molecules with unpaired electrons
Often add carbon-containing alkyl groupsOften base pair incorrectly, leading to transition or transversion mutations
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Nonalkylating agents—a variety of other chemicals can modify DNA structure
For example, nitrous acid and sodium nitrite can deaminate bases
Intercalating agents are planar polycyclic aromatic molecules that can distort DNA by inserting themselves between the stacked bases
Causes base pair deletion or insertionThe intercalating agent ethidium bromide is a fluorescent tag molecule used as a nucleic acid stain
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
DNA Structure: The Genetic MaterialDNA Structure: The Genetic MaterialIn the early decades of the twentieth century, life scientists believed that of the two chromosome components (DNA and protein) that protein was most likely responsible for transmission of inherited traits
The work of several scientists would lead to another conclusion
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
In 1928, Fred Griffith performed a remarkable set of experiments involving pneumococcal strains: smooth (S) and rough (R)
Identified the concept of transformation, though few accepted his discoveryFigure 17.9 Fred
Griffith’s Experiment
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
In 1944, Oswald Avery and colleagues reported the identification of Griffith’s transforming principle as DNA
Everyone was still not convincedIt was not until 1952, when Hershey and Chase demonstrated the different functions of protein and DNA with their T2 bacteriophage experiment, that DNA was accepted as the genetic material
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
The Hershey-Chase experiment confirmed DNA as the transforming principle
Figure 17.10 The Hershey-Chase Experiment
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Determining the structure of DNA became an obvious priority
Investigators including Linus Pauling, Maurice Wilkins, Rosalind Franklin, James Watson, and Francis Crick all worked toward this goal
Watson and Crick won the race for the double helix and published their findings in the journal Nature in 1953
They were awarded the Nobel Prize in chemistry in 1962
Section 17.1: DNA
Figure 17.1 The First Complete Structural Model of DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Information used to construct the model of DNA:
1. Chemical and physical dimensions of deoxyribose, nitrogenous bases, and phosphate2. 1:1 Ratios of adenine to thymine and cytosine to guanine (Chargaff’s rules)3. X-ray diffraction studies of Rosalind Franklin
Figure 17.11 X-Ray Diffraction Study of DNA by Rosalind Franklin and R. Gosling
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
4. Wilkins and Stokes diameter and pitch estimates from X-ray diffraction5. Linus Pauling’s recent demonstration that proteins could exist in a helical conformation
Figure 17.12 X-Ray Diffraction Study of DNA by Rosalind Franklin and R. Gosling
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
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