The DNA Molecule: The Molecular Basis of Inheritance the dna... · The DNA Molecule: The Molecular...

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

PowerPoint® Lecture Presentations for

BiologyEighth Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

Chapter 16

The DNA Molecule: The Molecular Basis of Inheritance

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Slide 2 The Structure of Nucleic Acids

• What are the nucleic acids monomers called?

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• What are the nucleic acid polymers called?

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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Slide 3 Fig. 5-27

5′ end

Nucleoside

Nitrogenousbase

Phosphategroup Sugar

(pentose)

Polynucleotide, or nucleic acid

3′ end

3′C

3′C

5′C

5′C

Nitrogenous basesPyrimidines

Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA)

Purines

Adenine (A) Guanine (G)

Sugars

Deoxyribose (in DNA) Ribose (in RNA)

Each nucleotide consists of a nitrogenous base, a pentose sugar, and a phosphate group

The nucleotide without the phosphate is called a nucleoside

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Fig. 5-UN6

Covalent bonds formed between the –OH group on the 3′ carbon of one nucleotide and the phosphate on the 5′carbon on the next

Backbone of sugar-phosphate units with nitrogenous bases as appendages

The sequence of bases along a DNA or mRNA polymer is unique for each gene

One DNA molecule includes many genes!

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Slide 5 Fig. 5-28

Sugar-phosphatebackbones

3' end

3' end

3' end

3' end

5' end

5' end

5' end

5' end

Base pair (joined byhydrogen bonding)

Old strands

Newstrands

Nucleotideabout to beadded to anew strand

Two polynucleotides spiraling around an imaginary axis form a Double Helix

What is meant by Antiparallel?

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Slide 6 Fig. 16-7

Hydrogen bond 3′ end

5′ end

3.4 nm

0.34 nm3′ end

5′ end

1 nm

Would you suspect the nitrogenous bases to be hydrophilic or hydrophobic?

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What DNA bases can pair up?

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How many DNA molecules do we have? _________

How many do bacteria have? _________

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Slide 8 Fig. 16-8

Cytosine (C)

Adenine (A) Thymine (T)

Guanine (G)

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Slide 9 1953: Watson and Crick Publish the Structure of DNA

One-page paper in the journal, Nature

- Structure of DNA suggests its function(DNA replication)

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copyingmechanism for the genetic material."Watson and Crick

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Fig. 16-6

(a) Rosalind Franklin (b) Franklin’s X-ray diffraction photograph of DNA

Maurice Wilkins and Rosalin Franklin were using X-ray crystallography to study molecular structure of DNA

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Slide 11 Fig. 16-10

Parent cellFirst replication

Second replication

(a) Conservative model

(b) Semiconserva-tive model

(c) Dispersive model

Which model is correct?

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Slide 12 Fig. 16-9-3

A T

GC

T A

TA

G C

(a) Parent molecule

A T

GC

T A

TAG C

(c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand

(b) Separation of strands

A T

GC

T A

TA

G C

A T

GC

T A

TAG C

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

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DNA Replication: A Closer Look

• The copying of DNA is remarkable in its speed and accuracy

• More than a dozen enzymes and other proteins participate in DNA replication

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

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Slide 14 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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Slide 15 Fig. 16-12a

Origin of replication Parental (template) strand

Daughter (new) strand

Replication forkReplication bubble

Double-stranded DNA molecule

Two daughter DNA molecules

Single origin of replication in E. coli

0.5 µm

Many bacteria have a single,circular chromosomes with one origin of replication

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Fig. 16-12b

0.25 µm

Origin of replication Double-stranded DNA molecule

Parental (template) strandDaughter (new) strand

Bubble Replication fork

Two daughter DNA molecules

Multiple origins of replication in eukaryotes

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Overview: 2 Different Things Going On1. Leading strand synthesis

2. Lagging strand synthesis

Leading strand

Leading strandLagging strand

Lagging strandOrigin of replication

Primer

Replication forks move in opposite

directions

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Slide 18 Leading Strand Synthesis

• 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

• Along one template strand of DNA, the DNA polymerase synthesizes a leading strand continuously, moving toward the replication fork


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Fig. 16-13

Topoisomerase

Helicase

PrimaseSingle-strand binding proteins

RNA primer

5′5′

5′ 3′

3′

3′

What function do each of these enzymes perform?

Replication Fork

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Slide 20 DNA polymerases can’t initiate synthesis of a polynucleotide; they can only add nucleotides to the 3′end

• The initial nucleotide strand is a short RNA primer

• 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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Slide 21 Fig. 16-15bOrigin of replication

RNA primer

“Sliding clamp”

DNA pol IIIParental DNA

3′

5′

5′

5′

5′

5′

5′

3′

3′

3′

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• Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate

• dATP supplies adenine to DNA and is similar to the ATP of energy metabolism

• The difference is in their sugars: dATP has deoxyribose while ATP has ribose

• As each monomer of dATP joins the DNA strand, it loses two phosphate groups as a molecule of pyrophosphate


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Slide 23 Fig. 16-14

A

C

T

G

G

G

GC

C C

C

C

A

A

A

T

T

New strand 5′ end

Template strand 3′ end 5′ end 3′ end

3′ end

5′ end5′ end

3′ end

BaseSugar

Phosphate

Nucleoside triphosphate

Pyrophosphate

DNA polymerase

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Slide 24

• 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


Lagging Strand Synthesis

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Fig. 16-16a

OverviewOrigin of replication

Leading strand

Leading strand

Lagging strand

Lagging strand

Overall directions of replication

12

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Slide 26 Fig. 16-16b1

Template strand

5′

5′3′

3′Enzyme?

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Template strand

5′

5′3′

3′

RNA primer 3′ 5′

5′

3′

1Enzyme?

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Fig. 16-16b3

Template strand

5′

5′3′

3′


5′

3′

1

13′

3′5′

5′

Okazaki fragment

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Template strand

5′

5′3′

3′


5′

3′

1

13′

3′5′

5′

Okazaki fragment

12

3′

3′

5′

5′

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Template strand

5′

5′3′

3′


5′

3′

1

13′

3′5′

5′

Okazaki fragment

12

3′

3′

5′

5′

12

3′

3′

5′

5′

Enzyme?

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Fig. 16-16b6

Template strand

5′

5′3′

3′


5′

3′

1

13′

3′5′

5′

Okazaki fragment

12

3′

3′

5′

5′

12

3′

3′

5′

5′

12

5′

5′

3′

3′

Overall direction of replication

Enzyme?

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Slide 32 Table 16-1

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Slide 33 Fig. 16-17

OverviewOrigin of replication

Leading strand

Leading strand

Lagging strand

Lagging strandOverall directions

of replication

Leading strand

Lagging strand

Helicase

Parental DNA

DNA pol III

Primer Primase

DNA ligase

DNA pol III

DNA pol I

Single-strand binding protein

5′

3′

5′

5′

5′

5′

3′

3′

3′

3′13 2

4

Describe this figure – What is each enzyme doing?

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The DNA Replication Complex

• The proteins that participate in DNA replication form a large complex, a “DNA replication machine”

• The DNA replication machine is probably stationary during the replication process

• Recent studies support a model in which DNA polymerase molecules “reel in” parental DNA and “extrude” newly made daughter DNA molecules


Animation: DNA Replication Review

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Slide 35 Proofreading and Repairing DNA

• Replication has an error rate at ~1 in 100,000 nucleotides, but DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides (only 1 in 10 billion errors occur following this process).

• In mismatch repair of DNA, repair enzymes correct errors in base pairing (usually just after replication)

• DNA can also 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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Slide 36

Nuclease

DNA polymerase

DNA ligase

Fig. 16-18

Describe the Steps in Nucleotide Excision Repair

What is a thymine dimer?Thymine Dimer

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Replicating the Ends of DNA Molecules

• Limitations of DNA polymerase create problems for the linear DNA of eukaryotic chromosomes

• The usual replication machinery provides no way to complete the 5′ ends of daughter DNA strands, so repeated rounds of replication produce shorter DNA molecules


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Slide 38 Fig. 16-19

Ends of parental DNA strands

Leading strandLagging strand

Lagging strand

Last fragment Previous fragment

Parental strand

RNA primer

Removal of primers and replacement with DNA where a 3′ end is available

Second round of replication

New leading strand

New lagging strand

Further rounds of replication

Shorter and shorter daughter molecules

5′

3′

3′

3′

3′

3′

5′

5′

5′

5′

Describe the shortening oflinear DNA molecules with eachround of replication.

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Slide 39 Fig. 16-20

• Eukaryotic chromosomal DNA molecules have at their ends nucleotide sequences called telomeres (stained dots above)• 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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• 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

• 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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Slide 41 Concept 16.3 A chromosome consists of a DNA molecule packed together with proteins• In Bacteria:

– The chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein

– the DNA is “supercoiled” and found in a region of the cell called the nucleoid

• In Eukaryotes:

– chromosomes have linear DNA molecules associated with a large amount of protein

– Chromatin is a complex of DNA and protein found in the nucleus of eukaryotic cells

– Histones are proteins that are responsible for the first level of DNA packing in chromatin


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DNA double helix (2 nm in diameter)

Nucleosome(10 nm in diameter)

Histones Histone tailH1

DNA, the double helix Histones Nucleosomes, or “beads on a string” (10-nm fiber)

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Fig. 16-21b

30-nm fiber

Chromatid (700 nm)

Loops Scaffold

300-nm fiber

Replicated chromosome (1,400 nm)

30-nm fiber Looped domains (300-nm fiber)

Metaphase chromosome

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Slide 44 Chromatin is organized (packed) into fibers

– 10-nm fiber:• DNA winds around histones to form nucleosome “beads”• Nucleosomes are strung together like beads on a string by

linker DNA

– 30-nm fiber• Interactions between nucleosomes cause the thin fiber to coil

or fold into this thicker fiber

– 300-nm fiber• The 30-nm fiber forms looped domains that attach to

proteins

– Metaphase chromosome• The looped domains coil further• The width of a chromatid is 700 nm


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Slide 45

• Most chromatin is loosely packed in the nucleus but condenses prior to cell division

• Loosely packed chromatin is called euchromatin

• Heterochromatin, or highly condensed chromatin is inaccessible to gene expression machinery

• Histones can undergo chemical modifications that result in changes in chromatin organization

– For example, phosphorylation of a specific amino acid on a histone tail affects chromosomal behavior during meiosis


Chromatin undergoes changes in its degree of packing during the cell cycle – it is dynamic

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The DNA Molecule: The Molecular Basis of Inheritance the dna... · The DNA Molecule: The Molecular...

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