1. Deoxyribonucleic Acid
The Molecular Basis of Inheritance
Who are these guys?

2. What is DNA? Primary source of genetic information
RNA can be used in some cases
Eukaryotic cells – multiple, linear chromosomes, found in nucleus
____________________________________________________________________
_____________ = separate extra-piece of circular DNA

3. Watson and Crick – 1953 Discovered the structure of DNA
Nobel prize in 1962 (with Wilkins)
Deduced that DNA was a ____________
Through observations of the X-ray crystallographic images of DNA from Rosalind Franklin

4. Erwin Chargaff – 1950’s
____________________________________________________________________
In any DNA:
___________________________________________________________

5. DNA Structure Monomers = nucleotides Nucleotide structure:
_________________
Sugar (deoxyribose)
Nitrogen base
_______________________________

6. Anti-parallel strands
Nucleotides in DNA on one side run ____________and the opposing side runs from ____________
This gives the DNA molecule “direction”
________________________run in opposite directions 5 3 3 5

7. Bonding in DNA 5 3 3 5 hydrogen bonds covalent bonds
….strong or weak bonds?
How do the bonds fit the mechanism for copying DNA?

8. Nitrogen Bases and Pairing in DNA –
Purines
_________
guanine (G)
Pyrimidines
thymine (T)
___________
Pairing
A : T
2 Hydrogen bonds
C : G
_______________

9. Semi-Conservative Replication
Replication of DNA
base pairing allows each strand to serve as a template for a new strand
_________________________________________________________

10. Prokaryotic DNA Replication
Replication moves in two directions.
______________________________

11. Eukaryotic DNA Replication
______________________

12. single-stranded binding proteins
Replication: 1st step
__________________
DNA is unwound by _______________________
Makes the replication fork
Helicase breaks the hydrogen bonds between the two strands separating them
Free nucleotides are present in the nucleus
single-stranded binding proteins
replication fork

13. Leading and Lagging Strands5 3 3 5
DNA polymerase III
leading strand 5 3 5 3 5 5 3
lagging strand 5 3 5 3 5 3 5
lagging strand
leading strand
growing
replication fork
growing
replication fork 5
leading strand
lagging strand 3 5 5 5

14. Replication: Leading Strand
____________________________________________________________________________
_______________________lays down the nucleotides 5’ to 3’ direction
Can only add nucleotides to 3 end of a growing DNA strand

15. Replication: Lagging Strand
Runs in the opposite direction of leading strand.
__________________________________________________________________________________
DNA polymerase lays down nucleotides from 5’ to 3’ direction forming fragments: Okazaki fragments
RNA primer is removed from the fragments and replaced with DNA nucleotides
_____________________

16. direction of replication
Replication fork
Animation
DNA polymerase
lagging strand 3’
RNA
primase
Okazaki fragments 5’ 5’
DNA ligase
SSB 3’ 5’ 3’
helicase
DNA polymerase 5’
leading strand 3’
direction of replication
SSB = single-stranded binding proteins

17. Houston, we have a problem!
Chromosome erosion
__________________________________________________________________
DNA polymerase I 5 3 3 5
growing
replication fork 3
DNA polymerase III 5
RNA 5
Loss of bases at 5 ends in every replication
chromosomes get shorter with each replication
limit to number of cell divisions? 3

18. Telomeres
_____________________________________________________________________________
limit to ~50 cell divisions 5 3 3 5
growing
replication fork 3
telomerase 5 5
Telomerase
_________________________
can add DNA bases at 5 end
different level of activity in different cells
high in stem cells & cancers -- Why?
TTAAGGG
TTAAGGG
TTAAGGG 3

19. Editing & proofreading DNA
Many different types of polymerases and nucleases
Cuts and removes abnormal bases
________________________________________
repairs mismatched bases
Reduces error rate to 1 in 10 billion

20. DNA replication on the lagging strand
RNA primer is added
_____________________________
serves as starter sequence for DNA polymerase III
HOWEVER short segments called Okazaki fragments are made because it can only go in a 5 3 direction 5 5 3 5 3 5 3 3
growing
replication fork 5 3
primase 5
DNA polymerase III
RNA 3

21. Replacing RNA primers with DNA
________________________
removes sections of RNA primer and replaces with DNA nucleotides
DNA polymerase I 5 3
ligase 3 5
growing
replication fork 3 5
RNA 5 3
__________________________________________________