dna structure cc
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Nucleic acids Nucleic acids An overview of structureAn overview of structure
These slides provides an introduction to the structure and function of nucleic acids (DNA and RNA) in relation to organisms, genes, gene expression and protein synthesis.
Dr. Momna Hejmadi, University of Bath
N.B. Some images used in these slides are from the textbooks listed and are not covered under the Creative Commons license as yet
DNA basics resources created by Dr. Momna Hejmadi, University of Bath, 2010, is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 2.0 UK: England & Wales License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/2.0/uk/ or send a letter to Creative Commons, 171 Second Street, Suite 300, San Francisco, California 94105, USA.
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Books:Biochemistry (3e) by D Voet & J VoetMolecular biology of the cell (4th ed) by Alberts et
alEssential Cell Biology by Alberts et al Life: The Science of Biology by Sadava et al (8th
ed )
Key websiteshttp://www.dnaftb.org/dnaftb/http://www.dnai.org/lesson/go/2166/1994http://www.thelifewire.comHistory, structure and forms of DNA
http://www.dnai.org/lesson/go/2166See document: ‘References: DNA Structure and FunctionSee document: ‘References: DNA Structure and Function
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Learning objectives
Understand the timeline of discoveries leading to elucidation of DNA structure
Describe / draw the structure of nucleotides
Understand the alternative DNA conformations
Understand RNA structure and diversity
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Timeline1869 F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
http://www.dnai.org/lesson/go/2166/1994
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Discovery of transforming principle1928 – Frederick Griffith – experiments with Streptococcus pneumoniae
Smooth (S) virulent strain (polysaccharide coat protects it from immune system)
Rough (R) nonvirulent strain(lacks the polysaccharide coat)
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Griffith experiment showing thatstrains can be transformed by ‘transforming principle’
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What is this transforming principle?
Bacterial transformation demonstrates transfer of genetic material
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
Avery, McCleod & McCarty- Transforming principle is DNA
1944
http://www.dnai.org/lesson/go/2166/1994
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Avery, MacLeod, McCarty Experiment
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Avery, MacLeod, McCarty Experiment
Transforming principle is Transforming principle is DNADNA
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
1949
Avery, McCleod & McCarty- Transforming principle is DNA
1944
Erwin Chargaff – base ratios
http://www.dnai.org/lesson/go/2166/1994
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E. Chargaff’s ratios
A = TC = G A + G = C + T
% GC constant for given species regardless of age, nutrition or tissue type
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
1952
Avery, McCleod & McCarty- Transforming principle is DNA
1944
Hershey-Chase ‘blender’ experiment
http://www.dnai.org/lesson/go/2166/1994
1949 Erwin Chargaff – base ratios
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
1949
Avery, McCleod & McCarty- Transforming principle is DNA
1944
Hershey-Chase ‘blender’ experiment1952
Erwin Chargaff – base ratios
1952 R Franklin & M Wilkins–DNA diffraction pattern
http://www.dnai.org/lesson/go/2166/1994
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X-ray diffraction patterns produced by DNA fibersRosalind Franklin and Maurice Wilkins
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
1952
Avery, McCleod & McCarty- Transforming principle is DNA
1944
Hershey-Chase ‘blender’ experiment
1952 Erwin Chargaff – base ratios
1952 R Franklin & M Wilkins–DNA diffraction pattern
1953 J Watson and F Crick – DNA structure solvedhttp://www.dnai.org/lesson/go/2166/1994
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The Watson-Crick Model: DNA is a double helix
In 1951 Watson learns about x-ray diffraction pattern projected by DNA
Erwin Chargaff’s experiments demonstrate that ratio of A and T are 1:1, and G and C are 1:1
Chemical structure of nucleotides were known (deoxyribose sugar, phosphate, and nitrogenous base)
Putting this together……
Watson and Crick, 1953, Nature, 171
….in 1953 James Watson and Francis Crick propose their double helix model of DNA structure
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1962 Nobel Prize in Physiology or Medicine for their discoveries concerning the molecular structure of nucleic
acids and its significance for information transfer in living material"
James WatsonFrancis Crick Maurice Wilkins
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Nucleotides
DNA RNA
Originally elucidated by Phoebus Levine and Alexander Todd in early 1950’s
2’-deoxy-D-ribose 2’-D-ribose
Made of 3 components1) 5 carbon sugar (pentose)2) nitrogenous base3) phosphate group
1) SUGARS
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2) NITROGENOUS BASES planar, aromatic, heterocyclic derivatives of purines/pyrimidines
adenine
uracil
thymine
cytosine
guanine
pyrimidinespurines
Note:Base carbons denoted as 1 etc Sugar carbons denoted as 1’ etc
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Nucleotide monomernucleotide = phosphate ester monomer of pentosedinucleotide - Dimer
Oligonucleotide – short polymer (<10)
Polynucleotide – long polymer (>10)
Nucleoside = monomer of sugar + base
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1) Phosphodiester bonds5’ and 3’ links to pentose sugar
2) N-glycosidic bonds
Links nitrogenous base to C1’ pentose in beta configuration
5’ – 3’ polynucleotide linkages
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3’ end
5’ end 5’ – 3’ polarity
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Structurally, purines (A and G) pair best with pyrimidines (T and C)
Thus, A pairs with T and G pairs with C, also explaining Chargaff’s ratios
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Essential features of B-DNA
• Right twisting • Double stranded
helix• Anti-parallel • Bases on the
inside (Perpendicular to axis)
• Uniform diameter (~20A)
• Major and minor groove
• Complementary base pairing
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A- DNAA- DNA B-DNAB-DNA Z-DNAZ-DNA
Helix Right-handed Right-handed Left-handed
Width Widest Intermediate NarrowestPlanes of bases
planes of the base pairs inclined to the helix axis
planes of the base pairs nearly perpendicular to the helix axis
planes of the base pairs nearly perpendicular to the helix axis
Central axis 6A hole along helix axis
tiny central axis no internal spaces
Major groove Narrow and deep
Wide and deep No major groove
Minor groove Wide and shallow
Narrow and deep
Narrow and deep
DNA conformationsDNA conformations
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Right-handed helix intermediate planes of the base pairs
nearly perpendicular to the helix axis
tiny central axis wide + deep major groove narrow + deep minor
groove
B-DNAB-DNA
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DNA conformations
Right-handed helix Widest planes of the base pairs
inclined to the helix axis 6A hole along helix axis narrow + deep major
groove Wide + shallow minor
groove
A- DNAA- DNA
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Left-handed helix Narrowest planes of the base pairs nearly
perpendicular to the helix axis no internal spaces no major groove narrow + deep minor groove
Z-DNAZ-DNADNA conformations
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AABB ZZ
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The tertiary structure is similar to DNA, but with several important differences:
• Single stranded but usually forms intra-molecular base pairs• major and minor grooves are less pronounced • Uracil instead of thymine • Structural, adaptor and transfer roles of RNA are all involved in decoding the information carried by DNA
RNA StructureRNA Structure
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Types of RNA in the human genomeTypes of RNA in the human genome
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Class of RNA Example types Function Ribosomal RNA 16,23,18,28S Ribosomal subunits
Transfer RNA 22 mitochondrial 49 cytoplasmic
mRNA binding
Small nuclear RNA(snRNA)
U1,U2,U4,U5 etc RNA splicing
Small nucleolar RNA (snoRNA)
U3,U8 etc rRNA modification and processing
microRNA (miRNA) >200 types Regulatory RNA
XIST RNA Inactivation of X chromosome
Imprinting associated RNA
H19 RNA Genomic imprinting
Antisense RNA >1500 types Suppression of gene expression
Telomerase RNA Telomere formation
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What you need to remember from What you need to remember from this lecture this lecture
Classic experiments that lead to the elucidation of DNA structureWatson-Crick B-DNA structure (linkages, 5’-3’ polarity)Other DNA conformationsTypes of RNA
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1. Try the problem from this link:http://www.dnaftb.org/dnaftb/19/concept/index.html
Self-test
2. Use the questions on the following slides
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What sugar is used in in a DNA monomer? A) 3'-deoxyribose
B) 5'-deoxyribose
C) 2'-deoxyribose
D) Glucose
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What is the base found in RNA but not DNA?
A) CytosineB) Uracil
C) Thymine D) Adenine E) Guanine
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What covalent bonds link nucleic acid monomers?
A) Carbon-Carbon double bondsB) Oxygen-Nitrogen Bonds
C) Carbon-Nitrogen bonds D) Hydrogen bonds
E) Phosphodiester bonds
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Each deoxyribonucleotide is composed of
A) 2'-deoxyribose sugar, Nitrogenous base, 5'- hydroxyl
B) 3'-deoxyribose sugar, Nitrogenous base, 5'- hydroxyl
C) 3'-deoxyribose sugar, Nitrogenous base, 5'- Phosphate
D) Ribose sugar, Nitrogenous base, 5'-hydroxylE) 2'-deoxyribose sugar, Nitrogenous base, 5'- phosphate