1. The Molecular Basis of Inheritance
Chapter 16
The Molecular Basis of Inheritance

2. Overview: Life’s Operating Instructions
In 1953, James Watson and Francis Crick introduced an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA
DNA, the substance of inheritance, 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
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3. Fig. 16-1
Figure 16.1 How was the structure of DNA determined?

4. When mixing heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic
This phenomenon is called transformation, now defined as a change in genotype and phenotype due to assimilation of foreign DNA
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5. EXPERIMENT RESULTS Mixture of heat-killed S cells and living R cells
Fig. 16-2
Mixture of heat-killed S cells and living R cells
EXPERIMENT
Living S cells (control)
Living R cells (control)
Heat-killed S cells (control)
RESULTS
Figure 16.2 Can a genetic trait be transferred between different bacterial strains?
Mouse dies
Mouse healthy
Mouse healthy
Mouse dies
Living S cells

6. Additional Evidence That DNA Is the Genetic Material
It was known that DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group
In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next
This evidence of diversity made DNA a more credible candidate for the genetic material
Animation: DNA and RNA Structure
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7. Chargaff’s rules state that in any species there is an equal number of A and T bases, and an equal number of G and C bases
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8. Sugar–phosphate backbone 5 end Sugar (deoxyribose) 3 end
Fig. 16-5
Sugar–phosphate backbone  end
Nitrogenous bases
Thymine (T)
Adenine (A)
Figure 16.5 The structure of a DNA strand
Cytosine (C)
Phosphate
DNA nucleotide
Sugar (deoxyribose)  end
Guanine (G)

9. 5 end Hydrogen bond 3 end 1 nm 3.4 nm 3 end 0.34 nm 5 end
Fig. 16-7a
5 end
Hydrogen bond
3 end
1 nm
3.4 nm
Figure 16.7 The double helix
3 end
0.34 nm
5 end
(a) Key features of DNA structure
(b) Partial chemical structure

10. The adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C)
The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C
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11. Adenine (A) Thymine (T) Guanine (G) Cytosine (C) Fig. 16-8
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 manifest in the double helix
Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material
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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
Animation: DNA Replication Overview
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14. A T C G T A A T G C (a) Parent molecule Fig. 16-9-1
Figure 16.9 A model for DNA replication: the basic concept

15. (b) Separation of strands
Fig A T A T C G C G T A T A A T A T G C G C
(a) Parent molecule
(b) Separation of strands
Figure 16.9 A model for DNA replication: the basic concept

16. (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

17. Animation: Origins of Replication
Getting Started
Replication begins at special sites called origins of replication, where the two DNA strands are separated, opening up a replication “bubble”
A eukaryotic 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
Animation: Origins of Replication
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18. Parental (template) strand
Fig a
Origin of replication
Parental (template) strand
Daughter (new) strand
Replication fork
Double-stranded DNA molecule
Replication bubble
0.5 µm
Two daughter DNA molecules
Figure Origins of replication in E. coli and eukaryotes
(a) Origins of replication in E. coli

19. Double-stranded DNA molecule
Fig b
Origin of replication
Double-stranded DNA molecule
Parental (template) strand
Daughter (new) strand
0.25 µm
Bubble
Replication fork
Figure Origins of replication in E. coli and eukaryotes
Two daughter DNA molecules
(b) Origins of replication in eukaryotes

20. At the end of each replication bubble is a replication fork, a Y-shaped region where new DNA strands are elongating
Helicases are enzymes that untwist the double helix at the replication forks
Single-strand binding protein binds to and stabilizes single-stranded DNA until it can be used as a template
Topoisomerase corrects “overwinding” ahead of replication forks by breaking, swiveling, and rejoining DNA strands
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21. Single-strand binding proteins
Fig
Primase
Single-strand binding proteins 3
Topoisomerase 5 3
RNA primer
Figure Some of the proteins involved in the initiation of DNA replication 5 5 3
Helicase

22. The initial nucleotide strand is a short RNA primer
DNA polymerases cannot initiate synthesis of a polynucleotide; they can only add nucleotides to the 3 end
The initial nucleotide strand is a short RNA primer
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23. An enzyme called primase can start an RNA chain from scratch and adds RNA nucleotides one at a time using the parental DNA as a template
The primer is short (5–10 nucleotides long), and the 3 end serves as the starting point for the new DNA strand
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24. Nucleoside triphosphate
Fig
New strand 5 end
Template strand 3 end
5 end
3 end
Sugar A T A T
Base
Phosphate C G C G G C G C
DNA polymerase
3 end A T A
Figure Incorporation of a nucleotide into a DNA strand T
3 end C
Pyrophosphate C
Nucleoside triphosphate
5 end
5 end

25. Antiparallel Elongation
The antiparallel structure of the double helix (two strands oriented in opposite directions) affects replication
DNA polymerases add nucleotides only to the free 3end of a growing strand; therefore, a new DNA strand can elongate only in the 5 to 3direction
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26. Animation: Leading Strand
Along one template strand of DNA, the DNA polymerase synthesizes a leading strand continuously, moving toward the replication fork
Animation: Leading Strand
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27. Animation: Lagging Strand
To elongate the other new strand, called the lagging strand, DNA polymerase must work in the direction away from the replication fork
The lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase
Animation: Lagging Strand
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28. Overall directions of replication
Fig a
Overview
Origin of replication
Leading strand
Lagging strand
Lagging strand 2 1
Leading strand
Figure 16.6 Synthesis of the lagging strand
Overall directions of replication

29. Table 16-1

30. Single-strand binding protein Overall directions of replication
Fig
Overview
Origin of replication
Leading strand
Lagging strand
Leading strand
Lagging strand
Single-strand binding protein
Overall directions of replication
Helicase
Leading strand 5
DNA pol III 3 3
Primer
Primase 5
Parental DNA 3
Figure A summary of bacterial DNA replication
DNA pol III
Lagging strand 5
DNA pol I
DNA ligase 4 3 5 3 2 1 3 5

31. Proofreading and Repairing DNA
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
In mismatch repair of DNA, repair enzymes correct errors in base pairing
DNA can be damaged by chemicals, radioactive emissions, X-rays, UV light, and certain molecules (in cigarette smoke for example)
In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DNA
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32. Nuclease DNA polymerase DNA ligase Fig. 16-18
Figure Nucleotide excision repair of DNA damage
DNA ligase

33. Eukaryotic chromosomal DNA molecules have at their ends nucleotide sequences called telomeres
Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules
It has been proposed that the shortening of telomeres is connected to aging
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34. If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce
An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells
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35. The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions
There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist
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36. Concept 16.3 A chromosome consists of a DNA molecule packed together with proteins
The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein
Eukaryotic chromosomes have linear DNA molecules associated with a large amount of protein
In a bacterium, the DNA is “supercoiled” and found in a region of the cell called the nucleoid
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37. Animation: DNA Packing
Chromatin is a complex of DNA and protein, and is found in the nucleus of eukaryotic cells
Histones are proteins that are responsible for the first level of DNA packing in chromatin
For the Cell Biology Video Cartoon and Stick Model of a Nucleosomal Particle, go to Animation and Video Files.
Animation: DNA Packing
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

38. Nucleosomes, or “beads on a string” (10-nm fiber)
Fig a
Nucleosome
(10 nm in diameter)
DNA double helix (2 nm in diameter) H1
Histone tail
Histones
Figure 16.21a Chromatin packing in a eukaryotic chromosome
DNA, the double helix
Histones
Nucleosomes, or “beads on a string” (10-nm fiber)

39. Looped domains (300-nm fiber) Metaphase chromosome
Fig b
Chromatid
(700 nm)
30-nm fiber
Loops
Scaffold
300-nm fiber
Figure 16.21b Chromatin packing in a eukaryotic chromosome
Replicated chromosome (1,400 nm)
30-nm fiber
Looped domains (300-nm fiber)
Metaphase chromosome

40. Loosely packed chromatin is called euchromatin
Most chromatin is loosely packed in the nucleus during interphase and condenses prior to mitosis
Loosely packed chromatin is called euchromatin
During interphase a few regions of chromatin (centromeres and telomeres) are highly condensed into heterochromatin
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41. Sugar-phosphate backbone
Fig. 16-UN2 G C A T T A
Nitrogenous bases G C
Sugar-phosphate backbone C G A T C G
Hydrogen bond T A