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Transcript
DNA Structure and Function
DNA explains it all
• Explains HOW chromosomes pass on
genes
• Chemical instructions
for building proteins
• Understanding structure
explains function
Recent understanding
Understanding genetic material
• Originally thought that proteins were
genetic material
– Diverse group of molecules
– Specific functions
• Didn’t know much about nucleic acids
– Small and uniform molecules
Model organisms
• Bacteria and Viruses
– Small genome
– Easily manipulated
– Prone to mutations
– Share genetic material
Viruses
•
•
•
•
Protein Coat
DNA/RNA
Hijack host cell
Transform
1928-Transformation
Fredrick Griffith
1952-Genetic material
Hershey-Chase
Structural model of DNA
• Race to come up with a model
• Watson and Crick compiled research from
different labs
• Used chemistry to make guesses about bonds
1950s-Chargaff’s rules
• % Adenine = % Thymine
• % Cytosine = %Guanine
1950s-Rosalind Franklin
• X-ray crystallography
Double Helix
• Sugar Phosphate backbone
• Paired nucleotides
• Hydrogen bonds hold bases
together
Nucleotides
Base Pairing
• Complimentary bases allows replication
and repair
3 models of replication
1958-Meselson and Stahl
• Switched between normal and heavy
nitrogen media
• New DNA strands were heavier than old
DNA Replication
• Semi-conservative
• Each strand is a template for new DNA
Origin of Replication
• Enzymes recognize site, separate strands
of DNA
– Bacteria have single, circular plasmid, one
origin
– Chromosomes have many sites
Elongation
• DNA polymerases align nucleotides with
complimentary bases
Anti-parallel
• Anti-parallel= strands run in opposite
directions
• Two different
“ends” to
nucleotide
5` 3`
•
•
•
•
Can only add new nucleotides to 3` end
Strand grows 5`3`
Leading strand
Lagging Strand
– Okazaki fragments
Primers
•
•
•
•
Polymerase can only add to existing chain
RNA Primer is created as a foundation
Leading strand needs one primer
Lagging strand needs a primer for each
segment
• RNA is then replaced by
DNA
The enzymes
•
•
•
•
Primase- creates RNA primer
DNA polymerase III- adds nucleotides
DNA polymerase I- replaces RNA primer
DNA ligase- bonds Okazaki fragments
together
• Helicase- untwists and separates strands
Replication Machine
• Replication enzymes
form a large complex
• Complex anchors to
nuclear matrix
• DNA moves through
enzymes
Proofreading DNA
• 1 error/ 100,000 base pairs
• Polymerases identify and remove
mismatched nucleotides
• Defect in mismatch repair enzymes is
linked to cancer
• Errors are reduced to 1/10 billion
Repairing DNA
• Nucleotide excision
• Thymine Dimers
– UV radiation
– Xeroderma pigmentosa
Telomeres
• No way to replace RNA primer at the 3`
end of chromosome (no 3` to attach on to)
• Each round of replication results in a
shorter chromosome
• Telomeres = repeated TTAAGGG
• Protect necessary genes from being
eroded
Aging
• Telomeres shorten each time a cell divides
• Once cell exhausts telomeres it dies
• Telomerase=enzyme that restores
telomeres
– Active in germ line cells
– Detected in cancer cells