1. DNA: The Molecular Basis of Inheritance

2. Building a Structural Model of DNA
After most biologists became convinced that DNA was the genetic material of life, the next challenge was to determine its structure.
Rosalind Franklin produced a picture of the DNA molecule by using a technique called X-ray crystallography Franklin produced a picture of the DNA molecule using this technique

3. Franklin’s X-ray diffraction photograph of DNA
LE 16-6
Rosalind Franklin
Franklin’s X-ray diffraction
photograph of DNA

4. Based on the images, two other scientists named Watson and Crick were able to determine that DNA molecules took a double helix shape.

5. LE 16-7 5 end Hydrogen bond 3 end 1 nm 3.4 nm 3 end 0.34 nm 5 end
Key features of DNA structure
Partial chemical structure
Space-filling model

6. Sugar–phosphate
backbone
Nitrogenous
bases
5 end
Thymine (T)
Adenine (A)
Cytosine (C)
Phosphate
DNA nucleotide
Sugar (deoxyribose)
3 end
Guanine (G)

7. Watson and Crick built models of a double helix to match to the X-rays and chemistry of DNA
The side strands, or “backbones” of the DNA molecule are made of a sugar (deoxyribose) paired with a phosphate.
The deoxyribose backbones are joined together by a series of molecules called nitrogenous bases.

8. Nitrogenous Bases There are two types of nitrogenous bases: Purines
Much wider
Include adenine and guanine
Pyramidines
Much narrower
Include cytosine and thymine

9. How do the four bases combine to form DNA? Purine + purine: too wide
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How do the four bases
combine to form DNA?
Purine + purine: too wide
Pyrimidine + pyrimidine: too narrow
Purine + pyrimidine: width
matches data from X-rays

10. Watson and Crick reasoned that the pairing was more specific –
Adenine paired only with Thymine
Guanine paired only with Cytosine

11. Base Pairing to a Template Strand
DNA is a double-helix molecule made of two intertwining strands.
The two strands of DNA are complementary, meaning each has a set of bases that corresponds with the other.
In DNA replication, the molecule is be separated into its two strands.
Two new strands can be made from these templates, duplicating the molecule.

12. The parent molecule has two complementary
strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.

13. The parent molecule has two complementary
strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.
The first step in replication is separation of the two DNA strands.

14. LE 16-9_3 The parent molecule has two complementary
strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.
The first step in replication is separation of the two DNA strands.
Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand.

15. LE 16-9_4 The parent molecule has two complementary
strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C.
The first step in replication is separation of the two DNA strands.
Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand.
The nucleotides are connected to form the sugar-phosphate back-
bones of the new strands. Each “daughter” DNA
molecule consists of one parental strand and one new strand.

16. Origins of Replication
Replication begins at special sites called origins of replication.
The two DNA strands are separated, opening up a replication “bubble”
Each chromosome may have hundreds or even thousands of origins of replication
Replication proceeds in both directions from each origin, until the entire molecule is copied

17. LE 16-12 Parental (template) strand 0.25 µm Origin of replication
Daughter (new) strand
Bubble
Replication fork
Two daughter DNA molecules
In eukaryotes, DNA replication begins at may sites
along the giant DNA molecule of each chromosome.
In this micrograph, three replication
bubbles are visible along the DNA
of a cultured Chinese hamster cell
(TEM).

18. Elongating the DNA Strand
Enzymes called DNA polymerases catalyze the elongation of new DNA.
The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells.

19. Proofreading and Repairing DNA
DNA polymerases also proofread newly made DNA, replacing any incorrect nucleotides.
Two types of repair:
In mismatch repair, the enzymes replace incorrect bases with the correct ones.
In nucleotide excision repair, enzymes cut out and replace entire stretches of DNA that are damaged.

20. Replicating the Ends of DNA Molecules
DNA polymerase has one significant limitation.
The enzyme has no way to complete one of the ends.
Every time the DNA is copied, it becomes a little shorter.
Cells will divide countless times over the lifespan of an organism. How can DNA be protected, given this limitation?

21. Eukaryotic chromosomal DNA molecules have at their ends repeating nucleotide sequences called telomeres.
Telomeres are DNA, but do not actually encode for any traits.
Telomeres do not prevent the shortening of DNA molecules, but they postpone it.

22. Eventually, the telomeres are worn down and essential genes begin to be lost from the chromosomes.
This is one of the hypothesized causes of aging.
An enzyme called telomerase catalyzes the lengthening of telomeres in stem cells.
This enzyme cannot be produced indefinitely due to an increasing risk of the cell growing uncontrollably (cancer)