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BB10006: Cell & Molecular biology
Dr. MV Hejmadi
Dr. JR Beeching (convenor)
Prof. RJ Scott
Prof. JMW Slack
Dr. Momna Hejmadi (bssmvh@bath.ac.uk)
Structure and function of nucleic acids
Books (any of these):Any bioscience textbook will do but my
favourites are Biochemistry (3e) by D Voet & J VoetMolecular biology of the cell (4th ed) by Alberts et alEssential Cell Biology by Alberts et al
Key websites http://www.dnaftb.org/dnaftb/ 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 athttp://www.bath.ac.uk/bio-sci/hejmadi/teaching%202005-06.htm
Lecture 1 - Outline How investigators pinpointed DNA as the genetic materialThe elegant Watson-Crick model of DNA structureForms of DNA (A, B, Z)
References: History, structure and forms of DNA
http://www.dnai.org/lesson/go/2166
Timeline1869 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
What is this transforming principle?
Bacterial transformation demonstrates transfer of genetic material
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
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
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
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
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
http://www.dnai.org/lesson/go/2166/1994
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
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
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 10 9 base pairsNumber of genes = 26 – 32,000 genes
Goal: to sequence the entire human nuclear genome
The human genomeThe human genome
Nuclear genome (3.2 Gbp) 24 types of chromosomes Y- 51Mb and chr1 -279Mbp
Mitochondrial genome
DNA in forensicswhat can a single human hair tell
you?
nuclear DNAnuclear DNAHair rootHair root
mitochondrial DNAmitochondrial DNAHair shaftHair shaft
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
2) NITROGENOUS BASES planar, aromatic, heterocyclic derivatives of purines/pyrimidines
adenine
uracil
thymine
cytosine
guanine
pyrimidines
purines
Note:Base carbons denoted as 1 etc Sugar carbons denoted as 1’ etc
Nucleotide monomernucleotide = phosphate ester monomer of pentosedinucleotide - Dimer
Oligonucleotide – short polymer (<10)
Polynucleotide – long polymer (>10)
Nucleoside = monomer of sugar + base
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
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
DNA conformations
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
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
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
B-DNAB-DNAA- DNAA- DNA Z-DNAZ-DNA
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
Maybe because RNA, not DNA, is prone to base-catalysed hydrolysis
Why has DNA evolved as the genetic material but not RNA?
linear
human chromosomes
Double stranded DNA
Genetic material may be DNA
Single stranded DNA
circular
linear
circularProkaryotesMitochondriaChloroplastsSome viruses(pox viruses)
Parvovirus
adeno-associated viruses
reoviruses
Double stranded RNA
Genetic material may be RNA
Single stranded RNA
Retroviruses like HIV
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
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'-hydroxylE) 2'-deoxyribose sugar, Nitrogenous base, 5'- phosphate
Recommended