BB10006: Cell & Molecular biology
Dr. MV Hejmadi
Dr. JR Beeching
(convenor)
Prof. RJ Scott
Prof. JMW Slack
Day Time
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Monday
Monday
Wednesday
Wednesday
Monday
Monday
Wednesday
Monday
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
9:15
14:15
11:15
11:15
9:15
14:15
11:15
9:15
Date
14.2.05
14.2.05
16.2.05
21.2.05
21.2.05
23.2.05
28.2.05
28.2.05
2.3.05
7.3.05
7.3.05
9.3.05
14.3.05
14.3.05
16.3.05
11.4.05
11.4.05
13.4.05
18.4.05
18.4.05
20.4.05
25.4.05
25.4.05
27.4.05
4.5.05
9.5.05
9.5.05
11.5.05
16.5.05
Place
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
ArtsLT
UniHall
ArtsLT
ArtsLT
UniHall
Lecturer
Topic
MVH
MVH
MVH
MVH
MVH
MVH
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JRB
JMWS
JMWS
JMWS
JMWS
RJS
RJS
RJS
Nucleic acids
Nucleic acids
Nucleic acids
Nucleic acids
Nucleic acids
Nucleic acids
Radiochemistry
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Genetic modification
Animal development
Animal development
Animal development
Animal development
Plant development
Plant development
Plant development
Dr. Momna Hejmadi
(bssmvh@bath.ac.uk)
Structure and function of nucleic acids
Books (any of these):
1)
2)
Biochemistry (2/3e) by D Voet & J Voet
Molecular biology of the cell (4th ed) by
Alberts et al
3)
Any biochemistry textbook
Key websites
1)
2)
http://www.dnai.org/lesson/go/2166/1994
http://molvis.sdsc.edu/dna/index.htm
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 at
http://www.bath.ac.uk/bio-sci/hejmadi/teaching%202004-05.htm
Lecture 1 - Outline
How investigators pinpointed DNA as
the genetic material
The elegant Watson-Crick model of
DNA structure
Forms 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/2166
Voet and Voet – Chapter 28
Timeline
1800’s
F Miescher - nucleic acids
1928
F. Griffith - Transforming principle
http://www.dnai.org/lesson/go/2166/1994
Discovery of transforming
principle

1928 – Frederick Griffith – experiments
with smooth (S) virulent strain
Streptococcus pneumoniae and
rough (R) nonvirulent strain
Griffith experiment
Griffith experiment

Bacterial transformation demonstrates
transfer of genetic material
What is this transforming
principle?
Timeline
1800’s
F Miescher - nucleic acids
1928
F. Griffith - Transforming principle
1944
Avery, McCleod & McCarty- Transforming
principle is DNA
http://www.dnai.org/lesson/go/2166/1994
Avery, MacLeod, McCarty
Experiment
Avery, MacLeod, McCarty
Experiment
Timeline
1800’s
F Miescher - nucleic acids
1928
F. Griffith - Transforming principle
1944
Avery, McCleod & McCarty- Transforming
principle is DNA
1949
Erwin Chargaff – base ratios
http://www.dnai.org/lesson/go/2166/1994
E. Chargaff’s ratios
A=T A+G=C+T
C=G
% GC constant for given species
Timeline
1800’s
F Miescher - nucleic acids
1928
F. Griffith - Transforming principle
1944
Avery, McCleod & McCarty- Transforming
principle is DNA
1949
Erwin Chargaff – base ratios
1952
Hershey-Chase ‘blender’ experiment
http://www.dnai.org/lesson/go/2166/1994
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
Hershey and Chase
experiments
Hershey and Chase
experiments
Timeline
1800’s
F Miescher - nucleic acids
1928
F. Griffith - Transforming principle
1944
Avery, McCleod & McCarty- Transforming
principle is DNA
1952
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
X-ray diffraction patterns produced by
DNA fibers – Rosalind Franklin and
Maurice Wilkins
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
Human genome project
Goal: to sequence the entire human nuclear genome
Public consortium
Headed by F Collins
Started in mid 80’s
Working draft
completed in 2001
Final sequence 2003
Celera Genomics
Headed by C Venter
Started in mid 90’s
Working draft
completed in 2001
Nature: Feb 2001
Science: Feb 2001
Human genome = 3.3 X 109 base pairs
Number of genes = 26 – 32,000 genes
DNA, gene, genome?
DNA = nucleic acid
Gene = segments of DNA that encode protein
Genome = 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 -
Nucleotides
Originally elucidated by Phoebus Levine and Alexander
Todd in early 1950’s
Made of 3 components
1) 5 carbon sugar (pentose)
2) nitrogenous base
3) phosphate group
1) SUGARS
DNA
2’-deoxy-D-ribose
RNA
2’-D-ribose)
2) NITROGENOUS BASES
planar, aromatic, hetercyclic derivatives of purines/pyrimidines
purines
pyrimidines
adenine
guanine
Note:
Base carbons denoted as 1 etc
Sugar carbons denoted as 1’ etc
cytosine
thymine
uracil
nucleotide = phosphate
ester monomer of
pentose
dinucleotide - Dimer
Oligonucleotide – short
polymer (<10)
Polynucleotide – long
polymer (>10)
Nucleoside = monomer
of sugar + base
Nucleotide
monomer
5’ – 3’ polynucleotide linkages
2) N-glycosidic bonds
Links nitrogenous base to C1’
pentose in beta configuration
1) Phosphodiester bonds
5’ and 3’ links to pentose sugar
5’ – 3’ polarity
5’ end
3’ end
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


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
Why DNA
evolved as the
genetic
material but not
RNA?
Maybe because
RNA but not
DNA is prone to
base-catalysed
hydrolysis
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
DNA conformations
B-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
DNA conformations
A DNA
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 BDNA 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
B DNA
DNA conformations
Z DNA
B-DNA forms a righthanded 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
a
dinucleotide.
The Z-DNA helix has a
larger pitch and is therefore
narrower than that of BDNA.
B-DNA has a wide and deep
major groove and a narrow
and deep minor groove,
whereas Z-DNA has a
B DNA
Types of RNA
Messenger RNA (mRNA): Codes for proteins
Transfer RNA (tRNA): Adaptor between
mRNA & amino acids
Ribosomal RNA (rRNA): Forms ribosome
core for translation
Heterogenous nuclear RNA (hn RNA)
Small nuclear RNA (sn RNA): involved in
post-transcriptional processing
Genetic material may be DNA
Double stranded DNA
linear
linear
human chromosomes
circular
Single stranded DNA
Prokaryotes
Mitochondria
Chloroplasts
Some viruses
(pox viruses)
adeno-associated viruses
circular
Parvovirus
Genetic material may be RNA
Double stranded RNA
Single stranded RNA
Retroviruses like HIV
reoviruses
RNA / DNA hybrids
e.g. during
retroviral
replication
What is the base found in
RNA but not DNA? ?
A) Cytosine
B) Uracil
C) Thymine
D) Adenine
E) Guanine
What covalent bonds link
nucleic acid monomers?
A) Carbon-Carbon double bonds
B) Oxygen-Nitrogen Bonds
C) Carbon-Nitrogen bonds
D) Hydrogen bonds
E) Phosphodiester bonds
What sugar is used in in a
DNA monomer?
A) 3'-deoxyribose
B) 5'-deoxyribose
C) 2'-deoxyribose
D) Glucose
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'-hydroxyl
E) 2'-deoxyribose sugar, Nitrogenous base, 5'phosphate