Download DNA Structure DNA Molecular Structure 5/29/2012 Chapter 4

5/29/2012
Chapter 4
Genetics and Cellular Function
•
•
•
•
DNA Structure
• DNA – threadlike molecule with
uniform diameter, but varied length
DNA and RNA – the nucleic acids
DNA replication
Genes and their action
DNA to Proteins
– How many in most human cells?
(a)
A
T
G
C
A
T
A
• Double helix
T
G
C
A
T
C
G
• Composed of Nucleotides
T
A
G
C
(b)
T
C
G
1. phosphate group
2. deoxyribose sugar
3. nitrogenous base
T
A
G
Sugar–phosphate
backbone
4-1
DNA Molecular Structure
4-2
(c)
Nitrogenous Bases of DNA
Purines
• DNA and other nucleic acids are
polymers (chains) of nucleotides
Adenine
NH2
N
• Each nucleotide consists of
– one sugar - deoxyribose
– one phosphate group
– one nitrogenous base
C
Hydrogen
bond
Sugar–phosphate
backbone
HC
N
H
C
C
C
N
P
O
O
CH2
OH
H H
H H
OH
Phosphate
NH2
H
Deoxyribose
N
C
C
N
–
–
–
–
Adenine (A)
Guanine (G)
Cytosine (C)
Thymine (T)
NH
N
Adenine (A)
Guanine (G)
Pyrimidines
H
C
NH2
CH3
C
HC
C
N
N
H
C
NH
N
H
O
Cytosine (C)
• DNA bases - ATCG
O
C
HC
C
O
Thymine (T)
O
O
C
N
H
CH
CH
Uracil (U)
(b)
Mitosis?
• Nitrogenous bases united by
hydrogen bonds
Mitosis: division of cells that results
in daughter cells with the same
the genetic information that the
original cell had.
G
C
T
• DNA base pairing
A–T
C–G
C
G
• Law of Complementary Base
Pairing
T
– one strand determines base
sequence of other
A
G
• Depending on which chromosome
– 50 to 250 million base pairs
CH
NH
C
NH2
C
–
–
C
C
N
HN
Complementary Base Pairing
N
C
CH
HN
C
C
H
CH
N
O
HO
O
• There are only four
nitrogenous bases
46
C
46
Hydrogen
bond
Sugar–phosphate
backbone
46
Sugar–phosphate
backbone
Tiny piece of DNA
Diploid 2n
Diploid 2 n
27-6
1
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DNA Replication
DNA Replication and Cell Cycle
• before cell divides, it must
must duplicate its DNA
(replication)
- so each new cell gets exact
copy of DNA
1. Helicase breaks
H bonds at replication
fork
2. DNA Polymerase
adds complimentary
nucleotides
Don’t forget Law of
Complementary
Base Pairing –
When does this occur during the
cell cycle?
3. DNA ligase joins
segments together
4-7
2 DNA each with ½ of original DNA = Semi-conservative
DNA Replication
Key:
Continuous
Incoming
nucleotides
replication
3-52
= Adenine
= Thymine
= Cytosine
= Guanine
(e)
Replication
fork
Parental DNA
(b)
DNA
polymerase
DNA polymerase
Discontinuous
Replication
fork
Old
(template)
strand
(a)
Newly
made
strand
DNA helicase
Key
A
C
Leading
strand
T
(c)
Gap in
replication
(d)
New strand
forming
Lagging
strand
DNA ligase
G
Old (template) strand
DNA of one
chromatid
DNA polymerase
Human Anatomy and Physiology, 7e
by Elaine Marieb & Katja Hoehn
Copyright © 2007 Pearson Education, Inc.,
publishing as Benjamin Cummings.
Mutations
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• DNA polymerase does make mistakes
– But:
– checks new base pairs and tends to fix mistakes
– result is only 1 error per 1 billion bases replicated
• mutations - changes in DNA structure due to
replication errors or environmental factors (radiation,
viruses, chemicals)
– some mutations = no problem/some kill the cell, turn
it cancerous or cause genetic defects in future
generations
4-12
2
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DNA Function
DNA Function
• Gene – segment of DNA that codes for a specific protein
• Make Proteins!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
• Gene – segment of DNA that codes for a specific protein
– humans have ~ 35,000
• 2% of total DNA
• other 98% is non-coding DNA
– plays role in chromosome structure
– regulation of gene activity (on-off sites)
– no function at all – “junk” DNA
– humans have ~ 35,000
• 2% of total DNA
• other 98% is non-coding DNA
– plays role in chromosome structure
– regulation of gene activity
– no function at all – “junk” DNA
4-13
4-14
Genetic Code
RNA: Structure and Function
• Millions of different proteins, all made from 20 amino acids,
– encoded by genes made of 4 nucleotides (A,T,C,G)
•
• Genetic code – Arrangement of nucleotides that code for
amino acid sequence of proteins
RNA
– Much smaller than DNA
- a single nucleotide chain
- Ribose sugar (not deoxyribose)
- No thymine nitrogenous base (replaced by Uracil)
i.e., nucleotides arrangement determines amino acid arrangement
• General: a DNA triplet – a sequence of 3 DNA nucleotides
will code for 1 amino acid
3 types of RNA
1. messenger RNA (mRNA) over 10,000 bases
2. ribosomal RNA (rRNA) 3.
3. transfer RNA (tRNA) 70 - 90 bases
– codon - the 3 base sequence in mRNA
•
Function
– interprets code in DNA
– uses those instructions for protein synthesis
4-15
4-16
From DNA to Protein
Overview of Protein Synthesis
• all body cells contain identical genes (except sex cells and
some immune cells)
Nuclear
envelope
• different genes are activated in different cells
Transcription
• Once activated a gene:
DNA
1. Makes messenger RNA (mRNA) – a mirror-image copy of the
gene is made
• migrates from the nucleus to cytoplasm
• its code is read by the ribosomes
mRNA
2. mRNA attaches to ribosomes (ribosomal RNA (rRNA) and
enzymes)
Ribosome
Translation
3. transfer RNA (tRNA) – delivers amino acids to the ribosome
4. ribosomes assemble amino acids in the order directed by codons
of mRNA
Polypeptide
4-17
Figure 3.33
3
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Transcription: RNA Polymerase
•
•
•
•
The enzyme that oversees mRNA synthesis
Starts at a promoter site
Breaks H bonds & unwinds DNA
Adds complementary nucleotides on DNA template
strand
– following Law of Complimentary Base Pairing
– Joins RNA nucleotides together to match DNA
coding strand
• Reads a termination signal to stop transcription
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Coding
strand
Termination signal
Promoter
Template
strand
Transcription unit
IRNA polymerase binds to
promoter and unwinds 16–18 base
pairs of the DNA template strand
RNA
polymerase
Unwound DNA
RNA polymerase
bound to promoter
RNA
nucleotides
mRNA
RNA
nucleotides
RNA
polymerase
mRNA synthesis begins
RNA polymerase moves down DNA;
mRNA elongates
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mRNA synthesis is terminated
DNA
(a)
mRNA transcript
Coding strand
RNA polymerase
Unwinding
of DNA
Rewinding of DNA
Template strand
RNA
nucleotides
mRNA
RNA-DNA
hybrid region
(b)
22
Figure 3.34
Nucleus
From DNA to Protein
Nuclear membrane
RNA polymerase
Nuclear pore
Nuclear
envelope
mRNA
Template strand
of DNA
Transcription
Released mRNA
DNA
Pre-mRNA
RNA Processing
mRNA
Ribosome
Translation
Polypeptide
Figure 3.33
Figure 3.36
4
5/29/2012
Nucleus
Nuclear membrane
Nucleus
Nuclear membrane
RNA polymerase
Nuclear pore
RNA polymerase
Nuclear pore
mRNA
mRNA
Template strand
of DNA
Polysome: mRNA binding
to ribosome
Template strand
of DNA
Released mRNA
1
1
After mRNA processing, mRNA
leaves nucleus and attaches to
ribosome, and translation begins.
After mRNA processing, mRNA
leaves nucleus and attaches to
ribosome, and translation begins.
Small ribosomal
subunit
Codon 15
Codon 16 Codon 17
Amino acids
Released mRNA
tRNA
Aminoacyl-tRNA
synthetase
Small ribosomal
subunit
Codon 15
Direction of
ribosome advance
Portion of mRNA
already translated
Codon 16 Codon 17
Direction of
ribosome advance
Portion of mRNA
already translated
Large
ribosomal
subunit
Large
ribosomal
subunit
Energized by ATP,
the correct amino
acid is attached to
each species of tRNA
by aminoacyl-tRNA
synthetase enzyme.
Figure 3.36
Figure 3.36
Nucleus
Nuclear membrane
Nucleus
Nuclear membrane
RNA polymerase
Nuclear pore
RNA polymerase
Nuclear pore
mRNA
mRNA
Template strand
of DNA
Template strand
of DNA
Amino acids
Released mRNA
1
After mRNA processing, mRNA
leaves nucleus and attaches to
ribosome, and translation begins.
Codon 16 Codon 17
1
tRNA
After mRNA processing, mRNA
leaves nucleus and attaches to
ribosome, and translation begins.
Aminoacyl-tRNA
synthetase
Small ribosomal
subunit
Codon 15
Amino acids
Released mRNA
tRNA
Aminoacyl-tRNA
synthetase
Small ribosomal
subunit
Codon 15
Direction of
ribosome advance
Portion of mRNA
already translated
Codon 16 Codon 17
Direction of
ribosome advance
Portion of mRNA
already translated
tRNA “head”
bearing
anticodon
tRNA “head”
bearing
anticodon
Large
ribosomal
subunit
2
Incoming aminoacyltRNA hydrogen bonds
via its anticodon to
complementary mRNA
sequence (codon) at
the A site on the
ribosome.
Large
ribosomal
subunit
Energized by ATP,
the correct amino
acid is attached to
each species of tRNA
by aminoacyl-tRNA
synthetase enzyme.
Energized by ATP,
the correct amino
acid is attached to
each species of tRNA
by aminoacyl-tRNA
synthetase enzyme.
Incoming aminoacyltRNA hydrogen bonds
via its anticodon to
complementary mRNA
sequence (codon) at
the A site on the
ribosome.
2
As the ribosome
moves along the
mRNA, a new amino
acid is added to the
growing protein chain
and the tRNA in the A
site is translocated
to the P site.
3
Figure 3.36
Figure 3.36
Translation of mRNA
Nucleus
Nuclear membrane
RNA polymerase
Nuclear pore
Cytosol
8
mRNA
Nucleus
DNA
Template strand
of DNA
Ribosomal subunits
rejoin to repeat the
process with the same
or another mRNA.
Amino acids
7
5
Released mRNA
mRNA
1
After mRNA processing, mRNA
leaves nucleus and attaches to
ribosome, and translation begins.
Codon 15
Codon 16 Codon 17
4
tRNA
1
Aminoacyl-tRNA
synthetase
Small ribosomal
subunit
mRNA leaves
the nucleus.
2 Ribosome
binds mRNA.
Direction of
ribosome advance
The preceding tRNA hands off
the growing protein to the new
tRNA, and the ribosome links the
new amino acid to the protein.
tRNA anticodon binds
to complementary
mRNA codon.
GU
Protein
A
CGU
C A U GC
3
Portion of mRNA
already translated
tRNA “head”
bearing
anticodon
Large
ribosomal
subunit
Once its amino acid is
released, tRNA is
ratcheted to the E site
and then released to
reenter the cytoplasmic
pool, ready to be
recharged with a new
amino acid.
3
As the ribosome
moves along the
mRNA, a new amino
acid is added to the
growing protein chain
and the tRNA in the A
site is translocated
to the P site.
ADP
tRNA
2
4
Incoming aminoacyltRNA hydrogen bonds
via its anticodon to
complementary mRNA
sequence (codon) at
the A site on the
ribosome.
Energized by ATP,
the correct amino
acid is attached to
each species of tRNA
by aminoacyl-tRNA
synthetase enzyme.
A
tRNA binds an
amino acid; binding
consumes 1 ATP.
ATP
6
+
After translating the
entire mRNA, the
ribosome dissociates
into its two subunits.
Pi
Free tRNA
tRNA is released from
the ribosome and is
available to pick up a
new amino acid and
repeat the process.
Free amino acids
4-30
Figure 3.36
5
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31
Protein Synthesis
Information Transfer from DNA to RNA
Template strand
Figure 3.38
Review of Peptide Formation
3-43
Genetic Code:
• RNA codons code for
amino acids
according to a
genetic code
• Remember there are
20 amino acids
1 DNA double helix
2 triplets on the
template strand of DNA
3 Corresponding codons of
mRNA transcribed from the
DNA triplets
4 The anticodons of tRNA that
bind to the mRNA codons
5 The amino acids carried by
those six tRNA molecules
6 The amino acids linked into a
peptide chain
4-35
Figure 3.35
6
5/29/2012
Protein Packaging and Secretion
Mechanism of Gene Activation
Prolactin
Prolactin
receptors
1
1
Exocytosis
Protein formed by
ribosomes on rough ER.
ATP
2 Protein packaged into transport
vesicle, which buds from ER.
Nucleus
Casein
7
3 Transport vesicles fuse into clusters that
unload protein into Golgi complex.
2
4 Golgi complex modifies
protein structure.
Secretory
vesicles
AD P
+
Pi
6
Golgi
complex
5 Golgi vesicle containing
finished protein is formed.
Regulatory
protein
(transcription
activator)
6 Secretory vesicles
release protein by
exocytosis.
Ribosomes
Clathrin-coated
transport vesicle
Golgi
complex
Rough
Endoplasmic
reticulum
5
3
Rough ER
4
Lysosome
Casein
gene
Figure 4.11
4-37
mRNA
for casein
RNA
polymerase
4-38
7