THE MOLECULAR
BASIS OF
INHERITANCE
BIF 13.1 – 13.3
What you must know
The structure of DNA.
The major steps to replication.
The difference between replication, transcription,
and translation.
The general differences between the bacterial
chromosome and eukaryotic chromosomes.
How DNA is packaged into a chromosome.
Problem:
Is the genetic material of organisms made of
DNA or proteins?
Frederick Griffith (1928)
Frederick Griffith (1928)
Conclusion: living R bacteria transformed into
deadly S bacteria by unknown, heritable
substance
Oswald Avery, et al. (1944)
Discovered that the transforming agent was
DNA (ruled out lipids, carbs, proteins,
RNA)
Hershey and Chase (1952)
Bacteriophages: virus that infects bacteria; composed of
DNA and protein
Protein = radiolabel S
DNA = radiolabel P
Hershey and Chase (1952)
Conclusion: DNA entered infected bacteria DNA must
be the genetic material!
Edwin Chargaff (1947)
Chargaff’s Rules:
DNA composition varies
between species
Ratios:
%A = %T and %G = %C
Rosalind Franklin (1950’s)
Worked with Maurice Wilkins
X-ray crystallography = images of DNA
Provided measurements on chemistry of DNA
James Watson & Francis Crick (1953)
Discovered the
double helix by
building models to
conform to
Franklin’s X-ray
data and
Chargaff’s Rules.
Structure of DNA
DNA = double helix
“Backbone” = sugar +
phosphate
“Rungs” = nitrogenous
bases
Structure of DNA
Nitrogenous Bases
Adenine (A)
purine
Guanine (G)
Thymine (T)
pyrimidine
Cytosine (C)
Pairing:
purine + pyrimidine
A=T
GΞC
Structure of DNA
Hydrogen bonds between base pairs of the two strands
hold the molecule together like a zipper.
Structure of DNA
Antiparallel: one strand (5’ 3’), other strand runs in
opposite, upside-down direction (3’ 5’)
DNA Comparison
Prokaryotic DNA Eukaryotic DNA
Double-stranded Double-stranded
Circular Linear
One chromosome Usually 1+ chromosomes
In cytoplasm In nucleus
No histones DNA wrapped around
Supercoiled DNA histones (proteins)
Forms chromatin
Problem:
How does DNA replicate?
Replication: Making DNA from existing DNA
3 alternative
models of DNA
replication
Meselson & Stahl
By LadyofHats - did myself based on the information in wikipedia plus the following
websites:[1], [2], [3], [4], [5] and [6], Public Domain,
https://commons.wikimedia.org/w/index.php?curid=4804985
Meselson & Stahl
Replication is semiconservative
DNA Replication Video
http://www.youtube.com/watch?v=4jtmOZaIvS
0&feature=related
Major Steps of Replication:
1. Helicase: unwinds DNA at origins of replication
2. Initiation proteins separate 2 strands forms replication bubble
3. Primase: puts down RNA primer to start replication
4. DNA polymerase III: adds complimentary bases to leading
strand (new DNA is made 5’ 3’)
5. Lagging strand grows in 3’5’ direction by the addition of
Okazaki fragments
6. DNA polymerase I: replaces RNA primers with DNA
7. DNA ligase: seals fragments together
1. Helicase unwinds DNA at origins of
replication and creates replication forks
3. Primase adds RNA primer
4. DNA polymerase III adds nucleotides in 5’3’
direction on leading strand (new DNA)
Replication on leading strand
Leading strand vs. Lagging strand
Okazaki Fragments:
Short segments of DNA
that grow 5’3’ that are
added onto the Lagging
Strand
DNA Ligase: seals
together fragments
Problem at the 5’ End
DNA poly only adds
nucleotides to 3’ end
No way to complete 5’
ends of daughter strands
Over many replications,
DNA strands will grow
shorter and shorter
Telomeres: repeated units of short nucleotide sequences
(TTAGGG) at ends of DNA
Telomeres “cap” ends of DNA to postpone erosion of genes
at ends (TTAGGG)
Telomerase: enzyme that adds to telomeres
Eukaryotic germ cells, cancer cells
Telomeres stained
orange at the ends of
mouse chromosomes
Telomeres & Telomerase
Proofreading and Repair
DNA polymerases proofread as bases added
Mismatch repair: special enzymes fix incorrect
pairings
Nucleotide excision repair:
Nucleases cut damaged DNA
DNA poly and ligase fill in gaps
Nucleotide Excision Repair
Errors:
Pairing errors: 1 in 100,000
nucleotides
Complete DNA: 1 in 10 billion
nucleotides
BioFlix: DNA Replication
http://media.pearsoncmg.com/bc/bc_0media_bi
o/bioflix/bioflix.htm?8apdnarep
