1. The Structure, Replication, and Chromosomal Organization of DNA
Chapter 8
The Structure, Replication, and Chromosomal Organization of DNA

2. History of DNA Discoveries
Friedrich Miescher Isolated nuclein from white blood cells 1869 Walter Flemming Named chromosomes for colored body 1882 Frederick Griffith Discovered transforming principle 1928 O.Avery, C.MacCleod, DNA is the transforming agent 1944 M.McCarty P.Levene, E.Chargaff, Discoveries of DNA components, ’s M.Wilkins, R.Franklin proportions, and positions J.Watson & F.Crick 3-D structure of DNA 1953 J. Watson Had his DNA sequenced 2008 Various organizations Human genome projects present

3. Discovery of a “transforming principle”
Frederick Griffiths, 1928
- English microbiologist
- Worked with Diplococcus pneumonia, which exists in two types
- Type S (Smooth) = Produces capsule
- Type R (Rough) = No capsule
- Capsule associated with virulence (Type S cause death and Type R does not)

4. Frederick Griffith’s Experiments demonstrated the transfer of genetic information (transforming principle)
Nathan H Lents, Ph.D. "DNA I: The Genetic Material," Visionlearning Vol. BIO (2),

5. DNA is that “genetic information”
protease
DNase
Work completed by
Avery, Macleod, &
MacCarty, 1944
Adapted from Nathan H Lents, Ph.D. "DNA I: The Genetic Material," Visionlearning Vol. BIO (2),

6. Summary of Early DNA Experiments
Transformation
The process of transferring genetic information (DNA) between cells
Transforming factor
The molecular agent of transformation; DNA

7. Elucidating the structure of DNA
Rosalind Franklin reasoned that the DNA is a helix with symmetrically organized subunits.

8. Elucidating the structure of DNA
James Watson and Francis Crick - Did not perform any experiments - Rather, they used the earlier research and inferences from model building with cardboard cutouts to solve the structure of DNA - proposed that DNA has two polynucleotide chains oriented in opposite directions, held together by hydrogen bonding to complementary bases in the opposite strand

9. DNA structure A single building block is a nucleotide
Each nucleotide is composed of:
- A deoxyribose sugar
- A phosphate group
- A nitrogenous base; one of four types
- Adenine (A), Guanine (G)
- Cytosine (C), Thymine (T)

10. Basic Chemistry: Nucleotides

11. DNA strand are antiparallel
The two polynucleotide chains in DNA run in opposite directions
Figure 8.9
The two polynucleotide chains in DNA run in opposite directions. The left strand runs 5′ to 3′, and the right strand runs 3′ to 5′. The base sequences in each strand are complementary. An A in one strand pairs with a T in the other strand, and a C in one strand is paired with a G in the opposite strand.
Fig. 8-9, p. 184

12. The Watson-Crick Model of DNA

13. Three Important Properties of the DNA Model
“A genetic material must carry out two jobs: duplicate itself and control the development of the rest of the cell in a specific way.”
- Francis Crick, 1953
Complementary strands provide a mechanism for DNA replication—each strand serves as a template for a new double helix

14. Semi-conservative DNA Replication
The two polynucleotide strands uncoil and each is a template for synthesis of a new strand

15. Proteins of DNA Replication
Helicase – unwinds the DNA strands
Primase – adds a short primer to each DNA strand
DNA polymerase – adds nucleotides to form new strands
Ligase – seals the fragments of the lagging strand
Pause and view DNA replication animation at:

16. The parent DNA double helix unwinds in this direction.
(b) Because DNA synthesis proceeds only in the 5’ to 3’direction, only one of the DNA strands can be assembled in a single piece.
The parent DNA double helix unwinds in this direction.
helicase
The other new DNA strand forms in short segments, which are called Okazaki fragments after the two scientists who discovered them. DNA ligase joins the fragments into a continuous strand of DNA.
3’ 5’
Only the leading DNA strand is assembled continuously. 3’
The lagging DNA strand is assembled in many pieces.
ligase
Figure 8.13
A close-up look at the process of DNA replication. (a) As the strands uncoil, bases are added to the newly synthesized strand by complementary base pairing with bases in template strand. The new bases are linked together by DNA polymerase. (b) DNA synthesis can proceed only in the 5′ → 3′ direction; newly synthesized DNA on one template strand is made in short segments and linked together by the enzyme DNA ligase.
polymerase
primase 3’ 5’ 5’ 3’
Fig. 8-13b, p. 188

17. 8.6 The Organization of DNA in Chromosomes
Each human chromosome
is a single DNA molecule…
does it ever get tangled?

18. Variation in Genome Sizes
Table 8-1, p. 184

19. Each DNA Molecule is Extensively Coiled to Allow it to Fit into the Nucleus

20. Structure of Nuclear Chromosomes
Chromatin
The complex of DNA and proteins that makes up a chromosome
Histones
DNA-binding proteins that help compact and fold DNA into chromosomes

21. Multiple levels of coiling of DNA and proteins
(b) When a chromosome is at its most condensed, the DNA is packed into tightly coiled coils.
Multiple levels of coiling of DNA and proteins
(c) When the coiled coils unwind, a molecule of chromosomal DNA and its associated proteins are organized as a cylindrical fiber.
Fiber
(d) A loosened fiber shows a “beads-on-a-string” organization. The “string” is the DNA molecule; each “bead” is the nucleosome.
Beads on
a string
Figure 8.16
A model of chromosomal structure beginning with a double-stranded DNA molecule. The DNA is first coiled around histones to form nucleosomes. The nucleosomes are coiled again and again into fibers that form the body of the chromosome. Chromosomes undergo cycles of coiling and uncoiling in mitosis and interphase, so their structure is dynamic.
DNA double helix
Core of histones
(e) A nucleosome consists of part of a DNA molecule looped twice around a core of histone proteins.
Nucleosome
Fig. 8-16b, p. 190

22. Centromeres and Telomeres are Specialized Chromosomal Regions
Centromeres attach to spindle fibers during mitosis
are chromosome tips composed of many repeats of TTAGGG tha shorten with each cell division (whether this is a cause or an effect of aging is debated)

23. Exploring Genetics: DNA for Sale
DNA marketing is being used to sell an ever-increasing number of products from jewelry containing DNA of celebrities to souvenir shirts printed with ink containing DNA of Olympic athletes