1. From Gene to Protein: Replication

2. All living things show similarities in chemical make-up and chemical activities
Cell
Nutrients are the same for all living things
Millions of products come from a finite number of building block molecules
DNA (blueprint)

3. Raw materials (nutrients) Blue print #1 (DNA genetic material)
Dog house (product)
Raw materials (nutrients)
Blue print # (DNA genetic material)
Tools (enzymes)

4. Blue Print #1 (DNA)
Blue Print #2 (DNA)

5. Nutrients same for all life Blue print (DNA) unique to each organism
Enzymes
Human products make human; dog products make a dog
Blue print (DNA) unique to each organism

6. let’s say that all genes code for proteins…
The “Central Dogma”
How do we move information from DNA to proteins?
translation
transcription
DNA
RNA
protein
For
simplicity sake,
let’s say that all genes code for proteins…
replication

7. From nucleus to cytoplasm…
Where are the genes?
genes are on chromosomes in nucleus
Where are proteins synthesized?
Proteins are made in cytoplasm by ribosomes
How does the information get from nucleus to cytoplasm?
shipped with
messenger RNA
nucleus

8. DNA Replication

9. Chromosomes and Inheritance
5/28/2019
I took the first quality X-ray diffraction images of DNA, and am credited with sparking the interests of both Watson and Crick in the question of DNA’s structure
Maurice Wilkins (1950)
Rosalind Franklin worked in my lab (and I had no idea!!)
G. Podgorski, Biol 1010

10. Better Pictures of DNA (1951)
Chromosomes and Inheritance
5/28/2019
Better Pictures of DNA (1951)
G. Podgorski, Biol 1010

11. Chromosomes and Inheritance
5/28/2019
Watson and Crick
1953 article in Nature
We figured it out
Now we’re famous!
G. Podgorski, Biol 1010

12. Chromosomes and Inheritance
5/28/2019
What’s So Special About DNA?
DNA is one of the most boring macromolecules imaginable - its made of only four building blocks and has a perfectly monotonous structure.
Worse yet, DNA just sits there - it doesn’t catalyze reactions or build the cell or organism.
So, what’s so good about DNA?
The answer lies in DNA’s ability to store and copy information.
G. Podgorski, Biol 1010

13. Chromosomes and Inheritance
5/28/2019
How Can DNA Store and Copy Information?
Key properties that allow these neat tricks are that DNA is a:
double stranded molecule ….
held together by complementary bases …..
… that pair through simple rules.
DNA is also capable of occasional change, and occasionally, change is good.
G. Podgorski, Biol 1010

14. Base pairing in DNA Purines Pyrimidines Pairing adenine (A)
guanine (G)
Pyrimidines
thymine (T)
cytosine (C)
Pairing
A : T
2 bonds
C : G
3 bonds

15. Chromosomes and Inheritance
5/28/2019
The Double Helix
Strand polarity
Strand complementarity
Antiparallel strands
G. Podgorski, Biol 1010

16. DNA Replication Hypotheses
Chromosomes and Inheritance
5/28/2019
DNA Replication Hypotheses
G. Podgorski, Biol 1010

17. Semiconservative DNA Replication
Chromosomes and Inheritance
5/28/2019
Semiconservative DNA Replication
G. Podgorski, Biol 1010

18. Semiconservative DNA Replication

19. Copying DNA Replication of DNA
base pairing allows each strand to serve as a template for a new strand
new strand is 1/2 parent template & 1/2 new DNA
semi-conservative copy process

20. Replication: 1st step Unwind DNA
helicase enzyme unwinds part of DNA helix
replication fork

21. Replication: 2nd step Build daughter DNA strand
add new complementary bases
Wih the help of DNA polymerase III
DNA
Polymerase III

22. Chromosomes and Inheritance
5/28/2019
Energy of Replication
The nucleotides arrive as nucleosides
DNA bases with P–P–P
P-P-P = energy for bonding
DNA bases arrive with their own energy source for bonding
bonded by enzyme: DNA polymerase III
ATP
GTP
TTP
CTP
G. Podgorski, Biol 1010

23. Leading & Lagging strands
Chromosomes and Inheritance
5/28/2019
Okazaki
Limits of DNA polymerase III
can only build onto 3 end of an existing DNA strand  5
Okazaki fragments 5 5 3 5 3 5 3
ligase
Lagging strand 3 3
growing
replication fork 5
Leading strand  3 5
Lagging strand
Okazaki fragments
joined by ligase
“spot welder” enzyme 3
DNA polymerase III
Leading strand
continuous synthesis
G. Podgorski, Biol 1010

24. Chromosomes and Inheritance
DNA polymerases
5/28/2019
Roger Kornberg
2006
DNA polymerase III
1000 bases/second!
main DNA builder
DNA polymerase I
20 bases/second
editing, repair & primer removal
Arthur Kornberg
1959
In 1953, Kornberg was appointed head of the Department of Microbiology in the Washington University School of Medicine in St. Louis. It was here that he isolated DNA polymerase I and showed that life (DNA) can be made in a test tube. In 1959, Kornberg shared the Nobel Prize for Physiology or Medicine with Severo Ochoa — Kornberg for the enzymatic synthesis of DNA, Ochoa for the enzymatic synthesis of RNA.
DNA polymerase III enzyme
G. Podgorski, Biol 1010

25. Fast & accurate!
It takes E. coli <1 hour to copy 5 million base pairs in its single chromosome
divide to form 2 identical daughter cells
Human cell copies its 6 billion bases & divide into daughter cells in only few hours
remarkably accurate
only ~1 error per 100 million bases
~30 errors per cell cycle

26. What does it really look like?1 2 3 4

27. Any Questions??