The DNA Molecule: The Molecular Basis of Inheritance the dna... · The DNA Molecule: The Molecular...
Transcript of The DNA Molecule: The Molecular Basis of Inheritance the dna... · The DNA Molecule: The Molecular...
Slide 1
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 2 The Structure of Nucleic Acids
• What are the nucleic acids monomers called?
_____________________________________
• What are the nucleic acid polymers called?
_______________________________________
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 4 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!
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 7
What DNA bases can pair up?
____________ and ____________
____________ and ____________
How many DNA molecules do we have? _________
How many do bacteria have? _________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 8 Fig. 16-8
Cytosine (C)
Adenine (A) Thymine (T)
Guanine (G)
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 10 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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 11 Fig. 16-10
Parent cellFirst replication
Second replication
(a) Conservative model
(b) Semiconserva-tive model
(c) Dispersive model
Which model is correct?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 13 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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
Animation: Origins of Replication
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 16 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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 17 Fig. 16-15a
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 19 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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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′
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 22
• 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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
Lagging Strand Synthesis
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 25 Fig. 16-16a
OverviewOrigin of replication
Leading strand
Leading strand
Lagging strand
Lagging strand
Overall directions of replication
12
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 26 Fig. 16-16b1
Template strand
5′
5′3′
3′Enzyme?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 27 Fig. 16-16b2
Template strand
5′
5′3′
3′
RNA primer 3′ 5′
5′
3′
1Enzyme?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 28 Fig. 16-16b3
Template strand
5′
5′3′
3′
RNA primer 3′ 5′
5′
3′
1
13′
3′5′
5′
Okazaki fragment
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 29 Fig. 16-16b4
Template strand
5′
5′3′
3′
RNA primer 3′ 5′
5′
3′
1
13′
3′5′
5′
Okazaki fragment
12
3′
3′
5′
5′
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 30 Fig. 16-16b5
Template strand
5′
5′3′
3′
RNA primer 3′ 5′
5′
3′
1
13′
3′5′
5′
Okazaki fragment
12
3′
3′
5′
5′
12
3′
3′
5′
5′
Enzyme?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 31 Fig. 16-16b6
Template strand
5′
5′3′
3′
RNA primer 3′ 5′
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?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 32 Table 16-1
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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?
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 34 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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
Animation: DNA Replication Review
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 36
Nuclease
DNA polymerase
DNA ligase
Fig. 16-18
Describe the Steps in Nucleotide Excision Repair
What is a thymine dimer?Thymine Dimer
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 37 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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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.
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 40
• 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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 42 Fig. 16-21a
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)
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 43 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
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
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
Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings
Chromatin undergoes changes in its degree of packing during the cell cycle – it is dynamic
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________