1. Molecular Basis of Inheritance
DNA Structure
DNA Replication

2. Evidence that DNA is the Hereditary Material of Life?
Griffith-Avery Experiment—DNA can transform bacteria
Hershey-Chase Experiment—Viral DNA can program cells
Chargaff—Analysis of DNA composition

3. Griffith-Avery Experiment: Transformation of Bacteria
2 strains of Streptococcus pneumonia
--S strain—pathogenic (disease-causing)
--R strain—non-pathogenic
-Griffith found that if he mixed heat-killed S-strain bacteria with the harmless strain, some of the living cells were converted to the pathogenic form (TRANSFORMATION—assimilation of external DNA)
-Avery purified various chemicals from the heat-killed pathogenic bacteria, only DNA worked to transform the cells
-Discovery met with criticism—most still believe protein is the hereditary material
Controls

4. Hershey-Chase Experiment: DNA, the Hereditary Material in Viruses
Bacteriophages—viruses that infect bacteria
--attach to host cell and inject their DNA into the cell
--experiment demonstrated that it was DNA, not protein, that functioned as the phage’s genetic material
Radioactively-labeled (sulfur) viral proteins remained outside the host cell during infection
Radioactively-labeled (phosphorus) viral DNA traveled inside the host cell
-the injected DNA molecules cause the cells to to produce new viral DNA and proteins

5. Chargaff:The Composition of DNA
Base composition of DNA varies between species
Regularity in ratios of nucleotide bases
Chargaff’s Rules: A = T and G = C
Adenine = 30.9%
Thymine = 29.4%
Guanine = 19.9%
Cytosine = 19.8%

6. Scientists in the Race for the Double Helix
Linus Pauling
James Watson
Francis Crick
Rosalind Franklin

7. Structure of DNA
Purines
Pyrimidines
Adenine
Thymine
Guanine
Cytosine

8. Structure of DNA DNA is a double helix with a uniform width
Purine and pyrimidine bases stacked

9. Purine + Pyrimidine: width consistent with X-ray data,
base ratios consistent with Chargaff’s rules: A = T and G  C

12. Structure of DNA is related to 2 primary functions:
1. Copy itself exactly for new cells that are created
2. Store and use information to direct cell activities

13. Complementary (Anti-Parallel) Strands of DNA
If one strand is known, the other strand can be determined 3’
= T 5’ A C G T
 G
 C
 C
= A
= T
= A
 G
 G 3’ 5’

14. DNA Replication: Semi-Conservative Model
2 strands of the parental DNA separate, and each functions as a template for the synthesis of a new complementary strand

15. DNA Replication
This replication process assures that daughter cells will carry the same genetic information as each other and as the parent cell.
Each daughter DNA has one old strand of DNA and one new strand of DNA

17. DNA Replication
Replication occurs simultaneously at many sites (replication bubbles) on a double helix
Allows DNA replication to occur in a shorter period of time

18. Elongating a New Strand
DNA polymerases can only attach nucleotides to the 3’ end of a growing daughter strand
Thus, replication always proceeds in the 5’ to 3’ direction

19. Priming DNA Synthesis Primase adds RNA primer to strand
DNA polymerase adds DNA nucleotides to strand
Another DNA polymerase replaces RNA with DNA

20. DNA Replication
Within the replication bubbles, one daughter strand is made continuously (leading strand) while the other daughter strand must be made in short pieces (lagging strand) which are then joined together by DNA ligase
These short pieces of DNA are called Okazaki fragments
Overall Direction of Replication-5’ to 3’

22. DNA Replication

25. Checking for Errors
1/1,000,000,000 chance of an error in DNA replication
Can lead to mutations
DNA polymerases have a “proofreading” role
Can only add nucleotide to a growing strand if the previous nucleotide is correctly paired to its complementary base
If mistake happens, DNA polymerase backtracks, removes the incorrect nucleotide, and replaces it with the correct base

26. Mismatch Repair
DNA polymerase proofreads each nucleotide and catches mistakes
The polymerase removes mistake and replaces with correct nucleotide

27. Excision Repair Nuclease
Used by skin cells when repairing genetic damage caused by UV rays of sunlight

28. End-Replication Problems

29. End-Replication Problems
Telomerase—enzyme lengthens telomeres (ends of nucleotide sequences)