dna structure cc

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Nucleic acids Nucleic acids An overview of An overview of structure 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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Page 1: DNA structure CC

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.

Page 2: DNA structure CC

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

Page 3: DNA structure CC

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

Page 4: DNA structure CC

Timeline1869 F Miescher - nucleic acids

1928 F. Griffith - Transforming principle

http://www.dnai.org/lesson/go/2166/1994

Page 5: DNA structure CC

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)

Page 6: DNA structure CC

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

Page 8: DNA structure CC

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

Page 9: DNA structure CC

Avery, MacLeod, McCarty Experiment

Page 10: DNA structure CC

Avery, MacLeod, McCarty Experiment

Transforming principle is Transforming principle is DNADNA

Page 11: DNA structure CC

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

Page 12: DNA structure CC

E. Chargaff’s ratios

A = TC = G A + G = C + T

% GC constant for given species regardless of age, nutrition or tissue type

Page 13: DNA structure CC

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

Page 14: DNA structure CC

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

Page 15: DNA structure CC

X-ray diffraction patterns produced by DNA fibersRosalind Franklin and Maurice Wilkins

Page 16: DNA structure CC

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

Page 17: DNA structure CC

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

Page 18: DNA structure CC

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

Page 20: DNA structure CC

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

Page 21: DNA structure CC

Nucleotide monomernucleotide = phosphate ester monomer of pentosedinucleotide - Dimer

Oligonucleotide – short polymer (<10)

Polynucleotide – long polymer (>10)

Nucleoside = monomer of sugar + base

Page 22: DNA structure CC

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

Page 23: DNA structure CC

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

Page 25: DNA structure CC

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

Page 26: DNA structure CC

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

Page 27: DNA structure CC

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

Page 28: DNA structure CC

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

Page 29: DNA structure CC

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

Page 34: DNA structure CC

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

Page 36: DNA structure CC

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

Page 38: DNA structure CC

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

Page 39: DNA structure CC

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