Transcript the nucleic acids

THE NUCLEIC
ACIDS
© 2007 Paul Billiet ODWS
Day 5 – Nucleic Acids

Do Now:




Draw a picture of an amino acid. Label all parts.
Draw a picture of the condensation reaction between two
amino acids forming a peptide bond
What influences the folding of protein? 2-3 sentences
Homework: Flashcards 26-32. Packet pgs. 15-17.
Exit Ticket
1. The complex structure of proteins can be explained in terms of four levels of structure,
primary, secondary, tertiary and quaternary.
(a)
Primary structure involves the sequence of amino acids that are bonded together to
form a polypeptide. State the name of the linkage that bonds the amino acids together.
(b)
Beta pleated sheets are an example of secondary structure. State one other example.
(c)
Tertiary structure in globular proteins involves the folding of polypeptides. State one
type of bond that stabilizes the tertiary structure.
2. Which is not a primary function of protein molecules?
A.
Hormones
B.
Energy storage
C.
Transport
D.
Structure
Proteins classified by function

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CATALYTIC: enzymes
STORAGE: ovalbumen (in eggs), casein (in milk), zein (in
maize)
TRANSPORT: haemoglobin
COMMUNICATION: hormones (eg insulin) and
neurotransmitters
CONTRACTILE: actin, myosin, dynein (in microtubules)
PROTECTIVE: Immunoglobulin, fibrinogen, blood clotting
factors
TOXINS: snake venom
STRUCTURAL: cell membrane proteins, keratin (hair),
collagen
Friedrich Miescher in 1869


Isolated what he called nuclein from the nuclei of
pus cells
Nuclein was shown to have acidic properties,
hence it became called nucleic acid
© 2007 Paul Billiet ODWS
Two types of nucleic acid are
found


Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)
© 2007 Paul Billiet ODWS
The distribution of nucleic
acids in the eukaryotic cell

DNA is found in the nucleus
with small amounts in mitochondria and chloroplasts

RNA is found throughout the cell

Ribosomes, tRNA, mRNA, etc.
© 2007 Paul Billiet ODWS
DNA as genetic material: The
circumstantial evidence
1.
2.
3.
4.
Present in all cells and virtually restricted to the nucleus
The amount of DNA in somatic cells (body cells) of any given species is
constant (like the number of chromosomes)
The DNA content of gametes (sex cells) is half that of somatic cells.
In cases of polyploidy (multiple sets of chromosomes) the DNA content
increases by a proportional factor
The mutagenic effect of UV light peaks at 253.7nm. The peak for the
absorption of UV light by DNA
© 2007 Paul Billiet ODWS
Introduction



The amino acid sequence of a polypeptide is
programmed by a gene.
A gene consists of regions of DNA, a polymer of
nucleic acids.
DNA (and their genes) is passed by the mechanisms
of inheritance.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
1. Nucleic acids store and transmit hereditary
information



There are two types of nucleic acids: ribonucleic
acid (RNA) and deoxyribonucleic acid (DNA).
DNA provides direction for its own replication.
DNA also directs RNA synthesis and, through RNA,
controls protein synthesis.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
 Organisms
 Each
inherit DNA from their parents.
DNA molecule is very long and usually consists
of hundreds to thousands of genes.
 When a cell reproduces itself by dividing, its DNA is
copied and passed to the next generation of cells.

While DNA has the information for all the cell’s
activities, it is not directly involved in the day to day
operations of the cell.



Proteins are responsible for implementing the instructions contained in
DNA.
Each gene along a DNA molecule directs the
synthesis of a specific type of messenger RNA
molecule (mRNA).
The mRNA interacts with the protein-synthesizing
machinery to direct the ordering of amino acids in a
polypeptide.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

The flow of genetic information is from DNA ->
RNA -> protein.
 Protein
synthesis occurs
in cellular structures
called ribosomes.
 In eukaryotes, DNA is
located in the nucleus,
but most ribosomes are
in the cytoplasm with
mRNA as an
intermediary.
Fig. 5.28
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
2. A nucleic acid strand is a polymer of
nucleotides


Nucleic acids are polymers of monomers called
nucleotides.
Each nucleotide consists of three parts: a nitrogen
base, a pentose sugar, and a phosphate group.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 5.29
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Mnemonics

CUT the Py(rimidines) (pie is a circle)

Many years AGo, it was important 2 get PUR(ine)
water
NUCLEIC ACID STRUCTURE


Nucleic acids are polynucleotides
Their building blocks are nucleotides
© 2007 Paul Billiet ODWS
NUCLEOTIDE STRUCTURE
PHOSPATE
SUGAR
Ribose or
Deoxyribose
BASE
PURINES
Adenine (A) Cytocine (C)
Guanine(G) Thymine (T)
Uracil (U)
NUCLEOTIDE
© 2007 Paul Billiet ODWS
PYRIMIDINES
Ribose is a pentose
C5
O
C1
C4
C3
© 2007 Paul Billiet ODWS
C2
Spot the difference
DEOXYRIBOSE
RIBOSE
CH2OH
O
C
H
H
H
C
OH
© 2007 Paul Billiet ODWS
OH
CH2OH
C
C
H
H
OH
O
C
H
H
C
C
C
OH
OH
H
H
Nucleic Acids

The subunits of Nucleic Acids are called:

Nucleotides

These are small molecules that are made out of
THREE even smaller molecules:
5 Carbon Sugar
 Phosphate Group
 Nitrogenous Base

5 Carbon Sugar
Phosphate Group
Nitogenous Base
Nucleic Acids

Nitrogenous Bases

A nucleotide can have one of five different bases
attached:
 Adenine
 Thymine
 Guanine
 Cytosine
 Uracil
 The
nitrogen bases, rings of carbon and
nitrogen, come in two types: purines and
pyrimidines.
 Pyrimidines
have a single six-membered ring.
 The three different pyrimidines, cytosine (C),
thymine (T), and uracil (U) differ in atoms attached
to the ring.
 Purine have a six-membered ring joined to a fivemembered ring.
 The two purines are adenine (A) and guanine (G).
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
 The
pentose joined to the nitrogen base is
ribose in nucleotides of RNA and
deoxyribose in DNA.
 The
only difference between the sugars is the lack of
an oxygen atom on carbon two in deoxyribose.
 The combination of a pentose and nucleic acid is a
nucleoside.
 The
addition of a phosphate group creates
a nucleoside monophosphate or nucleotide.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings


Polynucleotides are synthesized by connecting the
sugars of one nucleotide to the phosphate of the
next with a phosphodiester link.
This creates a repeating backbone of sugarphosphate units with the nitrogen bases as
appendages.





The sequence of nitrogen bases along a DNA or
mRNA polymer is unique for each gene.
Genes are normally hundreds to thousands of
nucleotides long.
The number of possible combinations of the four
DNA bases is limitless.
The linear order of bases in a gene specifies the
order of amino acids - the primary structure of a
protein.
The primary structure in turn determines threedimensional conformation and function.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Nucleic Acids

Complementary Base Pairing
 IN
DNA there are FOUR Bases.
 Because
DNA is double stranded the nitrogenous
bases pair with each other.
Adenine Pairs with Thymine
 Guanine Pairs with Cytosine

 IN
RNA there are FOUR Bases
 Because
RNA is made from DNA it also goes
through base pairing with other bases
Adenine Pairs with Uracil
 Guanine Pairs with Cytosine

Nucleic Acids


Another name for a Nucleic Acid is a polynucleotide.
Examples of Polynucleotides in the cell

DNA and RNA
Characteristic
DNA
RNA
Type of Sugar
Deoxyribose
Ribose
Nitrogenous Bases
Adenine, Thymine,
Guanine, Cytosine
Adenine, Uracil, Guanine ,
Cytosine
Number of Strands
2
1
Location in the Cell
Nucleus
Cytoplasm
Nucleic Acids
RN
A
DN
A
THE SUGAR-PHOSPHATE
BACKBONE
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The nucleotides are all
orientated in the same direction
The phosphate group joins the
3rd Carbon of one sugar to the 5th
Carbon of the next in line.
P
P
P
P
P
P
© 2007 Paul Billiet ODWS
P
G
ADDING IN THE BASES
P
C
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
The bases are attached
to the 1st Carbon
Their order is important
It determines the
genetic information of
the molecule
P
C
P
A
P
T
P
© 2007 Paul Billiet ODWS
T
DNA IS MADE OF TWO STRANDS OF
POLYNUCLEOTIDE
The sister strands of the DNA molecule run in opposite
directions (antiparallel)
 They are joined by the bases
 Each base is paired with a specific partner:
A is always paired with T
G is always paired with C
Purine with Pyrimidine
 This the sister strands are complementary but not
identical
 The bases are joined by hydrogen bonds, individually
weak but collectively strong

© 2007 Paul Billiet ODWS
Hydrogen bonds
P
DNA IS MADE OF
TWO STRANDS OF
POLYNUCLEOTIDE
G
C
P
P
C
G
P
P
A with T….TWO
G with C….THREE
C
G
P
P
A
T
P
P
T
A
P
P
© 2007 Paul Billiet ODWS
T
A
P
Erwin Chargaff’s Data (1950-51)
Wilkins & Franklin (1952): X-ray
crystallography
© Norman Collection on the History of Molecular Biology in Novato, CA
Purines & Pyrimidines
Adenine
Guanine
© 2007 Paul Billiet ODWS
Thymine
Cytosine
Watson & Crick Base pairing
© 2007 Paul Billiet ODWS
• Pairs pairs are held together by hydrogen bonds
• The two strings of DNA have to run anti-parallel in order to line up
the pairs
Cytosine
Guanine
Thymine
Adenine
The Double Helix (1953)
© Dr Kalju Kahn USBC Chemistry and Biochemistry
Public Domain image
3. Inheritance is based on replication of the
DNA double helix


An RNA molecule is single polynucleotide chain.
DNA molecules have two polynucleotide strands
that spiral around an imaginary axis to form a
double helix.

The double helix was first proposed as the structure of DNA in 1953 by
James Watson and Francis Crick.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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The sugar-phosphate backbones of the two
polynucleotides are on the outside of the helix.
Pairs of nitrogenous
bases, one from each
strand, connect the
polynucleotide chains
with hydrogen bonds.
Most DNA molecules
have thousands to
millions of base pairs.
Fig. 5.30
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Because of their shapes, only some bases are
compatible with each other.



Adenine (A) always pairs with thymine (T) and guanine (G) with cytosine
(C).
With these base-pairing rules, if we know the
sequence of bases on one strand, we know the
sequence on the opposite strand.
The two strands are complementary.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings


During preparations for cell division each of the
strands serves as a template to order nucleotides
into a new complementary strand.
This results in two identical copies of the original
double-stranded DNA molecule.


The copies are then distributed to the daughter cells.
This mechanism ensures that the genetic
information is transmitted whenever a cell
reproduces.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Quick Check – Hands Up!
Which substance is a base found in RNA?
A. Ribose
B. Thymine
C. Adenosine
D. Uracil
Quick Check – Hands Up!


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
Which base is connected to its complementary base in a
base pair by three hydrogen bonds?
A. Uracil
B. Thymine
C. Guanine
D. Adenine
Quick Check – Hands Up!
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Which molecule is found in both DNA and RNA?
A. Ribose
B. Uracil
C. Phosphate
D. Amino acid
Pair Share and Write – 2
Minutes

State the type of bonds that

(i) connect base pairs in a DNA molecule. (1)

(ii) link DNA nucleotides into a single strand. (1)
Think Aloud

(b) Distinguish between DNA and RNA nucleotides by
giving two differences in the chemical structure of the
molecules. (2)
4. We can use DNA and proteins as tape
measures of evolution



Genes (DNA) and their products (proteins)
document the hereditary background of an
organism.
Because DNA molecules are passed from parents to
offspring, siblings have greater similarity than do
unrelated individuals of the same species.
This argument can be extended to develop a
molecular genealogy between species.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Two species that appear to be closely-related based
on fossil and molecular evidence should also be
more similar in DNA and protein sequences than are
more distantly related species.


In fact, the sequence of amino acids in hemoglobin molecules differ by
only one amino acid between humans and gorilla.
More distantly related species have more differences.
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Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
CHAPTER 16
THE MOLECULE BASIS OF
INHERITANCE
Section B: DNA Replication and Repair
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Introduction


The specific pairing of nitrogenous bases in DNA
was the flash of inspiration that led Watson and
Crick to the correct double helix.
The possible mechanism for the next step, the
accurate replication of DNA, was clear to Watson
and Crick from their double helix model.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
1. During DNA replication, base pairing
enables existing DNA strands to serve as
templates for new strands

In a second paper Watson and Crick published their
hypothesis for how DNA replicates.


Essentially, because each strand is complementary to each other, each can
form a template when separated.
The order of bases on one strand can be used to add in complementary
bases and therefore duplicate the pairs of bases exactly.
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
When a cell copies a DNA molecule, each strand
serves as a template for ordering nucleotides into a
new complimentary strand.


One at a time, nucleotides line up along the template strand according to
the base-pairing rules.
The nucleotides are linked to form new strands.
Fig. 16.7
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
Watson and Crick’s model, semiconservative
replication, predicts that when a double helix
replicates each of the daughter molecules will have
one old strand and one newly made strand.
Fig. 16.8
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
Experiments in the late 1950s by Matthew Meselson
and Franklin Stahl supported the semiconservative
model, proposed by Watson and Crick, over the
other two models.



In their experiments, they labeled the nucleotides of the old strands with a
heavy isotope of nitrogen (15N) while any new nucleotides would be
indicated by a lighter isotope (14N).
Replicated strands could be separated by density in a centrifuge.
Each model: the semi-conservative model, the conservative model, and the
dispersive model, made specific predictions on the density of replicated
DNA strands.
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• The first replication in the 14N medium produced a band
of hybrid (15N-14N) DNA, eliminating the conservative
model.
• A second replication produced both light and hybrid
DNA, eliminating the dispersive model and supporting
the semiconservative model.
Fig. 16.9
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2. A large team of enzymes and other
proteins carries out DNA replication



It takes E. coli less than an hour to copy each of the 5
million base pairs in its single chromosome and
divide to form two identical daughter cells.
A human cell can copy its 6 billion base pairs and
divide into daughter cells in only a few hours.
This process is remarkably accurate, with only one
error per billion nucleotides.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings


The replication of a DNA molecule begins at
special sites, origins of replication.
In bacteria, this is a single specific sequence of
nucleotides that is recognized by the replication
enzymes.


These enzymes separate the strands, forming a replication “bubble”.
Replication proceeds in both directions until the entire molecule is
copied.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

In eukaryotes, there may be hundreds or thousands
of origin sites per chromosome.


At the origin sites, the DNA strands separate forming a replication
“bubble” with replication forks at each end.
The replication bubbles elongate as the DNA is replicated and eventually
fuse.
Fig. 16.10
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

DNA polymerases catalyze the elongation of new
DNA at a replication fork.
As nucleotides align with complementary bases
along the template strand, they are added to the
growing end of the new strand by the polymerase.


The rate of elongation is about 500 nucleotides per second in bacteria
and 50 per second in human cells.
The raw nucleotides are nucleoside triphosphates.

Each has a nitrogen base, deoxyribose, and a triphosphate tail.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

As each nucleotide is added, the last two phosphate
groups are hydrolyzed to form pyrophosphate.
Fig. 16.11
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

The strands in the double helix are antiparallel.
The sugar-phosphate backbones run in opposite
directions.


Each DNA strand has a 3’
end with a free hydroxyl
group attached to
deoxyribose and a 5’ end
with a free phosphate
group attached to
deoxyribose.
The 5’ -> 3’ direction of
one strand runs counter to
the 3’ -> 5’ direction of
the other strand.
Fig. 16.12
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



DNA polymerases can only add nucleotides to the
free 3’ end of a growing DNA strand.
A new DNA strand can only elongate in the 5’->3’
direction.
This creates a problem at the replication fork
because one parental strand is oriented 3’->5’ into
the fork, while the other antiparallel parental strand
is oriented 5’->3’ into the fork.
At the replication fork, one parental strand (3’-> 5’
into the fork), the leading strand, can be used by
polymerases as a template for a continuous
complimentary strand.
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

The other parental strand (5’->3’ into the fork), the
lagging strand,
is copied away from
the fork in short segments
(Okazaki fragments).
Okazaki fragments,
each about 100-200
nucleotides, are joined
by DNA ligase to form
the sugar-phosphate
backbone of a single
DNA strand.
Fig. 16.13
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

DNA polymerases cannot initiate synthesis of a
polynucleotide because they can only add
nucleotides to the end of an existing chain that is
base-paired with the template strand.
To start a new chain requires a primer, a short
segment of RNA.


The primer is about 10 nucleotides long in eukaryotes.
Primase, an RNA polymerase, links
ribonucleotides that are complementary to the DNA
template into the primer.

RNA polymerases can start an RNA chain from a single template strand.
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

After formation of the primer,
DNA polymerases can add
deoxyribonucleotides
to the 3’ end of the
ribonucleotide chain.
Another DNA
polymerase later
replaces the primer
ribonucleotides with
deoxyribonucleotides
complimentary to
the template.
Fig. 16.14
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



Returning to the original problem at the replication
fork, the leading strand requires the formation of
only a single primer as the replication fork
continues to separate.
The lagging strand requires formation of a new
primer as the replication fork progresses.
After the primer is formed, DNA polymerase can
add new nucleotides away from the fork until it
runs into the previous Okazaki fragment.
The primers are converted to DNA before DNA
ligase joins the fragments together.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings



In addition to primase, DNA polymerases, and
DNA ligases, several other proteins have
prominent roles in DNA synthesis.
A helicase untwists and separates the template
DNA strands at the replication fork.
Single-strand
binding proteins
keep the unpaired
template strands
apart during
replication.
Fig. 16.15
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

To summarize, at the replication fork, the leading
stand is copied continuously into the fork from a
single primer.
The lagging strand is copied away
from the fork in short segments,
each requiring a new primer.
Fig. 16.16
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Quick Check – Hands Up!
What are Okazaki fragments?
A. Short lengths of RNA primase attached to the
DNA during replication
B. Short sections of DNA formed during DNA
replication
C. Nucleotides added by DNA polymerase I in
the same direction as the replication fork
D. Sections of RNA removed by DNA
polymerase III and replaced with DNA
Quick Check – Hands Up!
Which enzyme catalyzes the elongation of the leading
strand?
[Source: image from W K Purves, et al., (2003) Life: The Science of Biology, 4, Sinauer Associates
(www.sinauer.com) and W H Freeman (www.whfreeman.com)]
A.
B.
C.
D.
RNA polymerase
Helicase
DNA polymerase
Ligase