1. Overview: Life’s Operating Instructions
DNA, the substance of heredity, is the most celebrated molecule of our time
Hereditary information is encoded in DNA and reproduced in “all” cells of the body
This DNA program directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits

2. Concept 16.1: DNA is the genetic material
Early in the 20th century, the identification of the molecules of inheritance loomed as a major challenge to biologists
The discovery of the genetic role of DNA began with research by Griffith in 1928
Griffith showed that bacteria contained a substance that could cause a genetic transformation
In 1944, Avery, McCarty and MacLeod announced that the transforming substance was DNA

3. More evidence for DNA as the genetic material came from studies of viruses that infect bacteria
Bacteriophages (or phages), are widely used in molecular genetics research
Simple systems that help to understand more complex ones: the “atom” of molecular biology

4. Bacteriophages were widely accepted as a model system
Consist of DNA and protein
Known to re-program genetics of infected cell

5. Alfred Hershey-Martha Chase “Blender” Experiment

6. In 1953, James Watson and Francis Crick introduced an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA
Figure 16.1 How was the structure of DNA determined?

7. Watson and Crick relied on other scientists’ data
Rosalind Franklin produced some of the important X ray crystallographic images

8. (c) Nucleoside components: sugars
5 end
Nitrogenous bases
Pyrimidines
5C
3C
Nucleoside
Nitrogenous
base
Cytosine (C)
Thymine (T, in DNA)
Uracil (U, in RNA)
Purines
Phosphate
group
Sugar
(pentose)
5C
Adenine (A)
Guanine (G)
3C
(b) Nucleotide
Sugars
3 end
Polynucleotide, or nucleic acid
- a polymer made of nucleotide monomers
Nucleotide = base + sugar + phosphate
Nucleoside = base + sugar
Deoxyribose (in DNA)
Ribose (in RNA)
(c) Nucleoside components: sugars

9. Sugar–phosphate backbone 5 end Sugar (deoxyribose) 3 end
Nitrogenous bases
The nucleotides are
linked by
phosphodiester
bonds
Thymine (T)
Adenine (A)
Cytosine (C)
Phosphate
DNA nucleotide
Sugar (deoxyribose)  end
Guanine (G)

10. Watson and Crick’s key contribution was the base-pair
5 end
Hydrogen bond
3 end
1 nm
3.4 nm
Figure 16.7 The double helix
For the Cell Biology Video Stick Model of DNA (Deoxyribonucleic Acid), go to Animation and Video Files.
For the Cell Biology Video Surface Model of DNA (Deoxyribonucleic Acid), go to Animation and Video Files.
3 end
0.34 nm
5 end
(a) Key features of DNA structure
(b) Partial chemical structure
(c) Space-filling model
Watson and Crick’s key contribution was the base-pair

11. Watson-Crick base pairs
Other types can form-and they do!
Adenine (A)
Thymine (T)
Figure 16.8 Base pairing in DNA
Guanine (G)
Cytosine (C)

12. Concept 16.2: Many proteins work together in DNA replication and repair
The relationship between structure and function is obvious in the double helix
Watson and Crick noted that the specific base pairing suggested a possible copying or replication mechanism for genetic material

13. The Basic Principle: Base Pairing to a Template Strand
Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication
In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules

14. (b) Separation of strands
Fig A T A T A T A T C G C G C G C G T A T A T A T A A T A T A T A T G C G C G C G C
(a) Parent molecule
(b) Separation of strands
(c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand
Figure 16.9 A model for DNA replication: the basic concept

15. Which Model?
Conservative (top)? Semi-conservative (middle)? Dispersive (bottom)? Meselson-Stahl experiment

16. The place on a DNA molecule where replication begins is an origin of replication or ori
Special sequence of DNA bases that signals the replication machinery to assemble
Many enzymes are involved: DNA helicase, DNA topoisomerase, DNA ligase.
The “growth point” is the replication fork

17. (a) Origin of replication in an E. coli cell
(b) Origins of replication in a eukaryotic cell
Origin of replication
Double-stranded DNA molecule
Parental (template) strand
Origin of replication
Daughter (new) strand
Parental (template) strand
Daughter (new) strand
Replication fork
Double- stranded DNA molecule
Replication bubble
Bubble
Replication fork
Two daughter DNA molecules
Two daughter DNA molecules
Figure Origins of replication in E. coli and eukaryotes.
0.5 m
0.25 m

18. DNA polymerase (Dpol) multiple types involved
Unidirectional enzyme (5’ to 3’ synthesis)
How to replicate both strands of the double helix at each replication fork?
The replication machinery has to go back and forth at each fork to copy both strands: leading strand and lagging strand.
Dpol enzymes not good at initiating-require help from RNA polymerase: primer

19. Overall directions of replication
DNA polymerase works in only one direction.
Overview
Leading strand
Origin of replication
Lagging strand
Lagging strand 2 1
Figure Synthesis of the lagging strand.
Leading strand
Overall directions of replication

20. Unidirectional enzyme has problems at the ends of a linear DNA template
Special adaptations required
Some systems have modifications to the ends of the linear DNA
More common-a special enzyme for synthesis of DNA ends is used: telomerase
A polymerase with a portable RNA template

21. Proofreading and Repair
DNA polymerases check their work as they go along and correct mistakes in real time: proofreading
Remaining mistakes are removed later by a separate system of enzymes: mismatch repair
Two important ways to ensure the integrity of DNA information