Lecture 1 – Molecular Structure of DNA and RNA and the
consequences (chapter 9)
- DNA – a central role in the Medical Sciences (genetic diseases, understanding cancer,
diagnostics, genetic therapies, research)
- Francis Crick – a biochemist, first to discover genetic material
- to fulfill its role, genetic material must meet several criteria: 1. information
2. transmission
3. replication
4. variation
- Friedrich Miescher – investigated the chemical composition of cells, including nucleus
– isolated an organic acid that was high in phosphorus, nitrogen, but
not sulfur – „nuclein“ – DNA
- Discovery of a „transforming prinicple“ – Frederick Griffith, 1928. :
- Streptoccocus pneumoniae infects mice - Pneumonia
- R Bacterium „rough coat“ – no inflammation
- S Bacterium „smooth coat“ – inflammation
- DNA is the ‘transforming principle’ allowing R bacteria to make a smooth coat and
allow infection
- Hershey and Chase results bacterio-phages
- viruses that infect bacteria
- consists of protein and DNA
- injecting their hereditary material into bacteria
- RNA can function as genetic material (in the case of viruses)
- A. Gierer and G. Schramm, 1956. – isolated RNA from the tobacco mosaic virus (TMV) –
a plant virus
- purified RNA caused the same lesions as intact TMV viruses – the viral genome is
composed of RNA
- each nucleotide consists of: 1. 2'-Deoxyribose (5 – carbon sugar)
2. phosphate group
3. a nitrogen – containing bases
- four bases: Adenine, Guanine, Thymine, Cytosine (there are more because bases can be
chemically modified, e.g. Methyl – C, HydroxyMethyl – C etc.)
- base + sugar – nucleoside
example: adenine + ribose = Adenosine
- base + sugar + phosphate(s) – nucleotide
example: Adenosine monophosphate (AMP)
- complementary bases pair: A and T
C and G
- Linus Pauling - hemoglobin: alpha helix, X-ray diffraction
,- Rosalind Franklin – used X – ray diffraction to study wet fibers of DNA
- Watson – Crick Model
- most DNAs consist of two nucleotide strands
- most DNA molecules are double-stranded
- nucleotides are connected by phosphodiester bonds; DNA backbone
- antiparallel strands
- hydrogen bonds between bases (base pairing)
- base ‘stacking’ provides most of the stability of double helix
- nucleotides are covalently linked together by phosphodiester bonds (a phosphate
connects the 5’ carbon of one nucleotide to the 3’ carbon of another), therefore the
strand has directionality / polarity > 5’ to 3’
- the phosphates and sugar molecules form the backbone of the nucleic acid strand (the
bases project from the backbone)
- DNA can form alternative types of helices
- the DNA double helix can form different types of secondary structure
- the predominant form found in living cells – B-DNA (right handed)
- under certain in vitro conditions – A-DNA and Z-DNA double helices can form
- DNA structure of chromosome ends (telomeres)
- DNA helix is associated with many kinds of proteins – chromatin
- RNA - the primary structure of a single-stranded RNA molecule is much like that of a
DNA molecule
- in RNA synthesis (transcription), only one of the two DNA strands is used as template
- several types of RNA: mRNA, tRNA, rRNA, microRNA etc.
- single strandedness – not a unique property of RNA
- RNA can fold into a 3D structure (like proteins)
- RNA lacks chemical diversity of proteins, but many conformational degrees of freedom
of its phosphate backbone
- unique hydrogen-bonding
- stacking of nucleotide bases
- intramolecular base pairing
- tertiary structure
, Lecture 2 – Transcription and RNA processing
(chapter 12)
− DNA replication: makes DNA copies that are transmitted from cell to cell and from
parent to offspring
− Transcription: produces an RNA copy of a gene
− Translation: produces a polypeptide using the information in mRNA
− Central Dogma of genetics: „… once (sequential) information has passed into protein it
cannot get out again.“ (F.H.C. Crick, 1958)
− a gene - the segment of DNA that contains the information to make a functional
product, which can be either a protein or an RNA
- the DNA base sequences define the beginning and end of a gene and determine
to a great extent the regulation of RNA synthesis (when, and how much, or in which cell
type a gene is transcribed)
− gene expression: the overall process by which the information within a gene results in
the production of a functional product (RNA / protein), causing a particular trait, in
conjunction with the environment
, − GENE EXPRESSION = RNA transcription + RNA processing (e.g. splicing, degradation) +
RNA translation (=protein synthesis) + protein degradation
− introns - a portion of a gene that does not code for amino acids
− exons - parts of the gene sequence that are expressed in the protein
Gene Expression regulation is dictated by the DNA sequence
− template strand – the strand that is actually transcribed (used as the template)
− coding strand (sense strand) – the opposite strand
− the base sequence of the coding strand is identical to that of the mRNA
transcript
− except for the substitution of uracil in RNA for thymine in DNA
− transcription factors recognize the promoter and regulatory sequences to control
transcription
− mRNA sequences such as the ribosomal-binding site and codons direct translation
