BB10006: Cell & Molecular biology
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Transcript of BB10006: Cell & Molecular biology
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BB10006: Cell & Molecular biologyDay Time Date Place Lecturer Topic
Monday 9:15 14.2.05 UniHall MVH Nucleic acidsMonday 14:15 14.2.05 ArtsLT MVH Nucleic acids
Wednesday 11:15 16.2.05 ArtsLT MVH Nucleic acidsMonday 9:15 21.2.05 UniHall MVH Nucleic acidsMonday 14:15 21.2.05 ArtsLT MVH Nucleic acids
Wednesday 11:15 23.2.05 ArtsLT MVH Nucleic acidsMonday 9:15 28.2.05 UniHall J RB RadiochemistryMonday 14:15 28.2.05 ArtsLT J RB Genetic modification
Wednesday 11:15 2.3.05 ArtsLT J RB Genetic modificationMonday 9:15 7.3.05 UniHall J RB Genetic modificationMonday 14:15 7.3.05 ArtsLT J RB Genetic modification
Wednesday 11:15 9.3.05 ArtsLT J RB Genetic modificationMonday 9:15 14.3.05 UniHall J RB Genetic modificationMonday 14:15 14.3.05 ArtsLT J RB Genetic modification
Wednesday 11:15 16.3.05 ArtsLT J RB Genetic modificationMonday 9:15 11.4.05 UniHall J RB Genetic modificationMonday 14:15 11.4.05 ArtsLT J RB Genetic modification
Wednesday 11:15 13.4.05 ArtsLT J RB Genetic modificationMonday 9:15 18.4.05 UniHall J RB Genetic modificationMonday 14:15 18.4.05 ArtsLT J RB Genetic modification
Wednesday 11:15 20.4.05 ArtsLT J RB Genetic modificationMonday 9:15 25.4.05 UniHall J RB Genetic modificationMonday 14:15 25.4.05 ArtsLT J MWS Animal development
Wednesday 11:15 27.4.05 ArtsLT J MWS Animal developmentWednesday 11:15 4.5.05 ArtsLT J MWS Animal development
Monday 9:15 9.5.05 UniHall J MWS Animal developmentMonday 14:15 9.5.05 ArtsLT RJ S Plant development
Wednesday 11:15 11.5.05 ArtsLT RJ S Plant developmentMonday 9:15 16.5.05 UniHall RJ S Plant development
Dr. MV Hejmadi
Dr. JR Beeching(convenor)
Prof. RJ Scott
Prof. JMW Slack
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Dr. Momna Hejmadi ([email protected])
Structure and function of nucleic acids
Books (any of these):1) Biochemistry (2/3e) by D Voet & J Voet2) Molecular biology of the cell (4th ed) by
Alberts et al3) Any biochemistry textbookKey websites 1) http://www.dnai.org/lesson/go/2166/19942) http://molvis.sdsc.edu/dna/index.htm
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Outline of my lectures
Lecture 1. Nucleic acids – an introduction
Lecture 2. Properties and functions of nucleic
acids
Lecture 3. DNA replication
Lectures 4-6. Transcription and translation
Access to web lectures athttp://www.bath.ac.uk/bio-sci/hejmadi/teaching%202004-05.htm
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Lecture 1 - Outline How investigators pinpointed DNA as the genetic materialThe elegant Watson-Crick model of DNA structureForms of DNA (A, B, Z etc)Types of nucleic acids (DNA and RNA)
References: History, structure and forms of DNA
http://www.dnai.org/lesson/go/2166Voet and Voet – Chapter 28
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Timeline1800’s F Miescher - nucleic acids
1928 F. Griffith - Transforming principle
http://www.dnai.org/lesson/go/2166/1994
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Discovery of transforming principle
1928 – Frederick Griffith – experiments with smooth (S) virulent strain Streptococcus pneumoniae and rough (R) nonvirulent strain
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Griffith experiment
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Griffith experiment
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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
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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
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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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Hershey and Chase experiments
1952 – Alfred Hershey and Martha Chase provide convincing evidence that DNA is genetic material
Waring blender experiment using T2 bacteriophage and bacteria
Radioactive labels 32P for DNA and 35S for protein
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Hershey and Chase experiments
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Hershey and Chase experiments
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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 solved
http://www.dnai.org/lesson/go/2166/1994
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X-ray diffraction patterns produced by DNA fibers – Rosalind Franklin and Maurice Wilkins
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The Watson-Crick Model: DNA is a double helix
1951 – James Watson learns about x-ray diffraction pattern projected by DNA
Knowledge of the chemical structure of nucleotides (deoxyribose sugar, phosphate, and nitrogenous base)
Erwin Chargaff’s experiments demonstrate that ratio of A and T are 1:1, and G and C are 1:1
1953 – James Watson and Francis Crick propose their double helix model of DNA structure
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Human genome project
Public consortiumHeaded by F CollinsStarted in mid 80’sWorking draft completed
in 2001Final sequence 2003Nature: Feb 2001
Celera GenomicsHeaded by C VenterStarted in mid 90’sWorking draft completed
in 2001
Science: Feb 2001
Human genome = 3.3 X 109 base pairsNumber of genes = 26 – 32,000 genes
Goal: to sequence the entire human nuclear genome
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DNA, gene, genome?DNA = nucleic acidGene = segments of DNA that encode proteinGenome = entire nucleic acid component of
any organism
Nucleic acids: made up of individual nucleotides linked together
Protein - polypeptides made up of individual amino acids linked together -
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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, hetercyclic derivatives of purines/pyrimidines
adenine
uracil
thymine
cytosine
guanine
pyrimidines
purines
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 bonds
5’ 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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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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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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Maybe because RNA but not DNA is prone to base-catalysed hydrolysis
Why DNA evolved as the genetic material but not RNA?
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B-DNA
Biologically dominant
Right-handed double helix
planes of base pairs are nearly perpendicular to the helix axis.
helix axis passes through the base pairs and hence B-DNA has no internal spaces B-DNA has a wide and deep major groove and a narrow and deep minor groove
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DNA conformationsB-DNA:
right-handed double helix with a wide and narrow groove.
A-DNA major groove is very deep and the minor groove is
quite shallow
Z-DNA consists of dinucleotides, each with different
conformations
4 stranded DNA Telomeric DNA
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DNA conformations
both form right-handed double helices
B-DNA helix has a larger pitch and hence a smaller width than
that of A
In B-DNA, the helix axis passes through the base pairs and hence
B-DNA has no internal spaces, whereas that of A-DNA has a 6
Angstrom diameter hole along its helical axis.
The planes of the base pairs in B-DNA are nearly perpendicular to the helix axis, whereas in A-DNA,
they are inclined from this. Therefore, B-DNA has a wide and deep major groove and a narrow and deep minor groove, whereas
A-DNA has a narrow and deep major groove, but a wide and
shallow minor groove.
A DNA B DNA
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DNA conformations
B-DNA forms a right-handed double helix in
which the repeating unit is a nucleotide,
whereas Z-DNA forms a left-handed double helix in which the repeating unit is
adinucleotide.
The Z-DNA helix has a larger pitch and is
therefore narrower than that of B-DNA.
B-DNA has a wide and deep major groove and a narrow and deep minor groove, whereas Z-DNA has a narrow and deep
minor groove but a nonexistent major groove.
B DNAZ DNA
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Types of RNAMessenger RNA (mRNA): Codes for proteinsTransfer RNA (tRNA): Adaptor between
mRNA & amino acidsRibosomal RNA (rRNA): Forms ribosome
core for translationHeterogenous nuclear RNA (hn RNA)Small nuclear RNA (sn RNA): involved in
post-transcriptional processing
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linear
human chromosomes
Double stranded DNA
Genetic material may be DNA
Single stranded DNA
circular
linear
circularProkaryotesMitochondriaChloroplastsSome viruses(pox viruses)
Parvovirus
adeno-associated viruses
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reoviruses
Double stranded RNA
Genetic material may be RNA
Single stranded RNA
Retroviruses like HIV
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RNA / DNA hybridse.g. during retroviral replication
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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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What sugar is used in in a DNA monomer?
A) 3'-deoxyribose
B) 5'-deoxyribose
C) 2'-deoxyribose
D) Glucose
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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