the central dogma of life l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
The Central Dogma of Life. PowerPoint Presentation
Download Presentation
The Central Dogma of Life.

Loading in 2 Seconds...

play fullscreen
1 / 51

The Central Dogma of Life. - PowerPoint PPT Presentation


  • 651 Views
  • Uploaded on

replication. The Central Dogma of Life. Protein Synthesis. The information content of DNA is in the form of specific sequences of nucleotides along the DNA strands The DNA inherited by an organism leads to specific traits by dictating the synthesis of proteins

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'The Central Dogma of Life.' - Faraday


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
protein synthesis
Protein Synthesis
  • The information content of DNA is in the form of specific sequences of nucleotides along the DNA strands
  • The DNA inherited by an organism leads to specific traits by dictating the synthesis of proteins
  • The process by which DNA directs protein synthesis, gene expression includes two stages, called transcription and translation
transcription and translation
Transcription and Translation
  • Cells are governed by a cellular chain of command
    • DNA RNA protein
  • Transcription
    • Is the synthesis of RNA under the direction of DNA
    • Produces messenger RNA (mRNA)
  • Translation
    • Is the actual synthesis of a polypeptide, which occurs under the direction of mRNA
    • Occurs on ribosomes
transcription and translation4

DNA

TRANSCRIPTION

mRNA

Ribosome

TRANSLATION

Polypeptide

(a)

Prokaryotic cell. In a cell lacking a nucleus, mRNAproduced by transcription is immediately translatedwithout additional processing.

Transcription and Translation
  • In prokaryotes transcription and translation occur together

Figure 17.3a

transcription and translation5

Nuclear

envelope

DNA

TRANSCRIPTION

Pre-mRNA

RNA PROCESSING

mRNA

Ribosome

TRANSLATION

(b)

Eukaryotic cell. The nucleus provides a separatecompartment for transcription. The original RNAtranscript, called pre-mRNA, is processed in various

ways before leaving the nucleus as mRNA.

Polypeptide

Transcription and Translation
  • In a eukaryotic cell the nuclear envelope separates transcription from translation
  • Extensive RNA processing occurs in the nucleus
transcription
Transcription
  • Transcription is the DNA-directed synthesis of RNA
  • RNA synthesis
    • Is catalyzed by RNA polymerase, which pries the DNA strands apart and hooks together the RNA nucleotides
    • Follows the same base-pairing rules as DNA, except that in RNA, uracil substitutes for thymine
slide7
RNA
  • RNA is single stranded, not double stranded like DNA
  • RNA is short, only 1 gene long, where DNA is very long and contains many genes
  • RNA uses the sugar ribose instead of deoxyribose in DNA
  • RNA uses the base uracil (U) instead of thymine (T) in DNA.

Table 17.1

synthesis of an rna transcript

1

3

2

Promoter

Transcription unit

5

3

3

5

Start point

DNA

RNA polymerase

Initiation. After RNA polymerase binds to

the promoter, the DNA strands unwind, and

the polymerase initiates RNA synthesis at the

start point on the template strand.

Template strand of DNA

5

3

3

5

Unwound

DNA

RNA

transcript

Elongation. The polymerase moves downstream, unwinding the

DNA and elongating the RNA transcript 5 3 . In the wake of

transcription, the DNA strands re-form a double helix.

Rewound

RNA

5

3

3

5

3

RNA

transcript

5

Termination. Eventually, the RNA

transcript is released, and the

polymerase detaches from the DNA.

5

3

3

5

3

5

Completed RNA transcript

Synthesis of an RNA Transcript
  • The stages of transcription are
    • Initiation
    • Elongation
    • Termination
slide9

Eukaryotic promoters

1

TRANSCRIPTION

DNA

Pre-mRNA

RNA PROCESSING

mRNA

Ribosome

TRANSLATION

Polypeptide

Promoter

5

3

A

T

A

T

A

A

A

A

T

A

T

T

T

T

3

5

TATA box

Start point

Template

DNA strand

Several transcription

factors

2

Transcription

factors

5

3

3

5

Additional transcription

factors

3

RNA polymerase II

Transcription factors

3

5

5

3

5

RNA transcript

Transcription initiation complex

Synthesis of an RNA Transcript - Initiation

  • Promoters signal the initiation of RNA synthesis
  • Transcription factors help eukaryotic RNA polymerase recognize promoter sequences
  • A crucial promoter DNA sequence is called a TATA box.
synthesis of an rna transcript elongation

Non-template

strand of DNA

Elongation

RNA nucleotides

RNA

polymerase

T

A

C

C

A

T

A

T

C

3

U

3 end

T

G

A

U

G

G

A

G

E

A

C

C

C

A

5

A

A

T

A

G

G

T

T

Direction of transcription

(“downstream”)

5

Template

strand of DNA

Newly made

RNA

Synthesis of an RNA Transcript - Elongation
  • RNA polymerase synthesizes a single strand of RNA against the DNA template strand (anti-sense strand), adding nucleotides to the 3’ end of the RNA chain
  • As RNA polymerase moves along the DNA it continues to untwist the double helix, exposing about 10 to 20 DNA bases at a time for pairing with RNA nucleotides
synthesis of an rna transcript termination
Synthesis of an RNA Transcript - Termination
  • Specific sequences in the DNA signal termination of transcription
  • When one of these is encountered by the polymerase, the RNA transcript is released from the DNA and the double helix can zip up again.
slide13

Post Termination RNA Processing

  • Most eukaryotic mRNAs aren’t ready to be translated into protein directly after being transcribed from DNA. mRNA requires processing.
  • Transcription of RNA processing occur in the nucleus. After this, the messenger RNA moves to the cytoplasm for translation.
  • The cell adds a protective cap to one end, and a tail of A’s to the other end. These both function to protect the RNA from enzymes that would degrade
  • Most of the genome consists of non-coding regions called introns
    • Non-coding regions may have specific chromosomal functions or have regulatory purposes
    • Introns also allow for alternative RNA splicing
  • Thus, an RNA copy of a gene is converted into messenger RNA by doing 2 things:
    • Add protective bases to the ends
    • Cut out the introns
alteration of mrna ends

A modified guanine nucleotide

added to the 5 end

50 to 250 adenine nucleotides

added to the 3 end

TRANSCRIPTION

DNA

Polyadenylation signal

Protein-coding segment

Pre-mRNA

RNA PROCESSING

5

3

mRNA

G

P

P

AAA…AAA

P

AAUAAA

Ribosome

Start codon

Stop codon

TRANSLATION

Poly-A tail

5 Cap

5 UTR

3 UTR

Polypeptide

Alteration of mRNA Ends
  • Each end of a pre-mRNA molecule is modified in a particular way
    • The 5 end receives a modified nucleotide cap
    • The 3 end gets a poly-A tail
rna processing splicing
RNA Processing - Splicing
  • The original transcript from the DNA is called pre-mRNA.
  • It contains transcripts of both introns and exons.
  • The introns are removed by a process called splicing to produce messenger RNA (mRNA)
rna processing splicing16

Intron

Exon

5

Exon

Intron

Exon

3

5 Cap

Poly-A tail

Pre-mRNA

TRANSCRIPTION

DNA

30

31

104

105

146

1

Pre-mRNA

RNA PROCESSING

Introns cut out and

exons spliced together

Coding

segment

mRNA

Ribosome

TRANSLATION

5 Cap

Poly-A tail

mRNA

Polypeptide

1

146

3 UTR

3 UTR

RNA Processing - Splicing
  • Ribozymes are catalytic RNA molecules that function as enzymes and can splice RNA
  • RNA splicing removes introns and joins exons

Figure 17.10

rna processing

3

1

2

RNA transcript (pre-mRNA)

5

Intron

Exon 1

Exon 2

Protein

Other proteins

snRNA

snRNPs

Spliceosome

5

Spliceosome

components

Cut-out

intron

mRNA

5

Exon 1

Exon 2

RNA Processing
  • RNA Splicing can also be carried out by spliceosomes
alternative splicing of exons
Alternative Splicing (of Exons)
  • How is it possible that there are millions of human antibodies when there are only about 30,000 genes?
  • Alternative splicing refers to the different ways the exons of a gene may be combined, producing different forms of proteins within the same gene-coding region
  • Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in higher eukaryotes
rna processing19

Gene

DNA

Exon 1

Exon 2

Intron

Exon 3

Intron

Transcription

RNA processing

Translation

Domain 3

Domain 2

Domain 1

Polypeptide

RNA Processing
  • Proteins often have a modular architecture consisting of discrete structural and functional regions called domains
  • In many cases different exons code for the different domains in a protein

Figure 17.12

translation

DNA

TRANSCRIPTION

mRNA

Ribosome

TRANSLATION

Polypeptide

Amino

acids

Polypeptide

tRNA with

amino acid

attached

Ribosome

Trp

Phe

Gly

tRNA

C

C

C

G

G

Anticodon

A

A

A

A

G

G

G

U

G

U

U

U

C

Codons

5

3

mRNA

Translation
  • Translation is the RNA-directed synthesis of a polypeptide
  • Translation involves
    • mRNA
    • Ribosomes - Ribosomal RNA
    • Transfer RNA
    • Genetic coding - codons
the genetic code

Gene 2

DNA

molecule

Gene 1

Gene 3

DNA strand

(template)

5

3

A

C

C

T

A

A

A

C

C

G

A

G

TRANSCRIPTION

A

U

C

G

C

U

G

G

G

U

U

U

5

mRNA

3

Codon

TRANSLATION

Gly

Protein

Phe

Trp

Ser

Amino acid

The Genetic Code
  • Genetic information is encoded as a sequence of nonoverlapping base triplets, or codons
  • The gene determines the sequence of bases along the length of an mRNA molecule
the genetic code22
The Genetic Code
  • Codons: 3 base code for the production of a specific amino acid, sequence of three of the four different nucleotides
  • Since there are 4 bases and 3 positions in each codon, there are 4 x 4 x 4 = 64 possible codons
  • 64 codons but only 20 amino acids, therefore most have more than 1 codon
  • 3 of the 64 codons are used as STOP signals; they are found at the end of every gene and mark the end of the protein
  • One codon is used as a START signal: it is at the start of every protein
  • Universal: in all living organisms
the genetic code23

Second mRNA base

U

C

A

G

U

UAU

UUU

UCU

UGU

Tyr

Cys

Phe

UAC

UUC

UCC

UGC

C

U

Ser

UUA

UCA

UAA

Stop

Stop

UGA

A

Leu

UAG

UUG

UCG

Stop

UGG

Trp

G

CUU

CCU

U

CAU

CGU

His

CUC

CCC

CAC

CGC

C

C

Arg

Pro

Leu

CUA

CCA

CAA

CGA

A

Gln

CUG

CCG

CAG

CGG

G

Third mRNA base (3 end)

First mRNA base (5 end)

U

AUU

ACU

AAU

AGU

Asn

Ser

C

lle

AUC

ACC

AAC

AGC

A

Thr

A

AUA

ACA

AAA

AGA

Lys

Arg

Met or

start

G

AUG

ACG

AAG

AGG

U

GUU

GCU

GAU

GGU

Asp

C

GUC

GCC

GAC

GGC

G

Val

Ala

Gly

GUA

GCA

GAA

GGA

A

Glu

GUG

GCG

GAG

GGG

G

The Genetic Code
  • A codon in messenger RNA is either translated into an amino acid or serves as a translational start/stop signal
transfer rna

3

A

Amino acid

attachment site

C

C

5

A

C

G

C

G

C

G

U

G

U

A

A

U

U

A

U

C

G

*

G

U

A

C

A

C

A

*

A

U

C

C

*

G

*

U

G

U

G

G

*

G

A

C

C

G

*

C

A

G

*

U

G

*

*

G

A

G

C

Hydrogen

bonds

(a)

Two-dimensional structure. The four base-paired regions and three loops are characteristic of all tRNAs, as is the base sequence of the amino acid attachment site at the 3 end. The anticodon triplet is unique to each tRNA type. (The asterisks mark bases that have been chemically modified, a characteristic of tRNA.)

G

C

U

A

G

*

A

*

A

C

*

U

A

G

A

Anticodon

Transfer RNA
  • Consists of a single RNA strand that is only about 80 nucleotides long
  • Each carries a specific amino acid on one end and has an anticodon on the other end
  • A special group of enzymes pairs up the proper tRNA molecules with their corresponding amino acids.
  • tRNA brings the amino acids to the ribosomes,

The “anticodon” is the 3 RNA bases that matches the 3 bases of the codon on the mRNA molecule

transfer rna25

Amino acid

attachment site

5

3

Hydrogen

bonds

A

A

G

3

5

Anticodon

Anticodon

(c)

Symbol used

in the book

(b) Three-dimensional structure

Transfer RNA
  • 3 dimensional tRNA molecule is roughly “L” shaped
ribosomes

DNA

TRANSCRIPTION

mRNA

Ribosome

TRANSLATION

Polypeptide

Exit tunnel

Growing

polypeptide

tRNA

molecules

Large

subunit

E

P

A

Small

subunit

5

3

mRNA

Computer model of functioning ribosome. This is a model of a bacterial ribosome, showing its overall shape. The eukaryotic ribosome is roughly similar. A ribosomal subunit is an aggregate of ribosomal RNA molecules and proteins.

(a)

Ribosomes
  • Ribosomes facilitate the specific coupling of tRNA anticodons with mRNA codons during protein synthesis
  • The 2 ribosomal subunits are constructed of proteins and RNA molecules named ribosomal RNA or rRNA
ribosome

P site (Peptidyl-tRNA

binding site)

A site (Aminoacyl-

tRNA binding site)

E site

(Exit site)

Large

subunit

E

P

A

mRNA

binding site

Small

subunit

Schematic model showing binding sites. A ribosome has an mRNA binding site and three tRNA binding sites, known as the A, P, and E sites. This schematic ribosome will appear in later diagrams.

(b)

Ribosome
  • The ribosome has three binding sites for tRNA
    • The P site
    • The A site
    • The E site
building a polypeptide

Growing polypeptide

Amino end

Next amino acid

to be added to

polypeptide chain

tRNA

3

mRNA

Codons

5

(c)

Schematic model with mRNA and tRNA. A tRNA fits into a binding site when its anticodon base-pairs with an mRNA codon. The P site holds the tRNA attached to the growing polypeptide. The A site holds the tRNA carrying the next amino acid to be added to the polypeptide chain. Discharged tRNA leaves via the E site.

Building a Polypeptide
building a molecule of trna

ATP loses two P groups

and joins amino acid as AMP.

2

3

Appropriate

tRNA covalently

Bonds to amino

Acid, displacing

AMP.

4

Activated amino acid

is released by the enzyme.

Building a Molecule of tRNA
  • A specific enzyme called an aminoacyl-tRNA synthetase joins each amino acid to the correct tRNA

Amino acid

Aminoacyl-tRNA

synthetase (enzyme)

Active site binds the

amino acid and ATP.

1

Adenosine

P

P

P

ATP

Adenosine

P

Pyrophosphate

P

Pi

Pi

Pi

Phosphates

tRNA

Adenosine

P

AMP

Aminoacyl tRNA

(an “activated

amino acid”)

Figure 17.15

building a polypeptide30
Building a Polypeptide
  • We can divide translation into three stages
    • Initiation
    • Elongation
    • Termination
  • The AUG start codon is recognized by methionyl-tRNA or Met
  • Once the start codon has been identified, the ribosome incorporates amino acids into a polypeptide chain
  • RNA is decoded by tRNA (transfer RNA) molecules, which each transport specific amino acids to the growing chain
  • Translation ends when a stop codon (UAA, UAG, UGA) is reached
initiation of translation

Large

ribosomal

subunit

P site

5

3

U

C

A

Met

Met

3

A

5

G

U

Initiator tRNA

GDP

GTP

E

A

mRNA

5

5

3

3

Start codon

mRNA binding site

Small

ribosomal

subunit

Translation initiation complex

2

1

The arrival of a large ribosomal subunit completes

the initiation complex. Proteins called initiation

factors (not shown) are required to bring all the

translation components together. GTP provides

the energy for the assembly. The initiator tRNA is

in the P site; the A site is available to the tRNA

bearing the next amino acid.

A small ribosomal subunit binds to a molecule of

mRNA. In a prokaryotic cell, the mRNA binding site

on this subunit recognizes a specific nucleotide

sequence on the mRNA just upstream of the start

codon. An initiator tRNA, with the anticodon UAC,

base-pairs with the start codon, AUG. This tRNA

carries the amino acid methionine (Met).

Initiation of Translation
  • The initiation stage of translation brings together mRNA, tRNA bearing the first amino acid of the polypeptide, and two subunits of a ribosome
elongation of the polypeptide chain

1

Codon recognition. The anticodon

of an incoming aminoacyl tRNA

base-pairs with the complementary

mRNA codon in the A site. Hydrolysis

of GTP increases the accuracy and

efficiency of this step.

Amino end

of polypeptide

DNA

TRANSCRIPTION

mRNA

Ribosome

TRANSLATION

Polypeptide

E

mRNA

3

Ribosome ready for

next aminoacyl tRNA

P

A

site

site

5

GTP

2

GDP

2

E

E

P

A

P

A

2

Peptide bond formation. An

rRNA molecule of the large

subunit catalyzes the formation

of a peptide bond between the

new amino acid in the A site and

the carboxyl end of the growing

polypeptide in the P site. This step

attaches the polypeptide to the

tRNA in the A site.

GDP

Translocation. The ribosome

translocates the tRNA in the A

site to the P site. The empty tRNA

in the P site is moved to the E site,

where it is released. The mRNA

moves along with its bound tRNAs,

bringing the next codon to be

translated into the A site.

3

GTP

E

P

A

Elongation of the Polypeptide Chain
  • In the elongation stage, amino acids are added one by one to the preceding amino acid
termination of translation

Release

factor

Free

polypeptide

5

3

3

3

5

5

Stop codon

(UAG, UAA, or UGA)

The release factor hydrolyzes

the bond between the tRNA in

the P site and the last amino

acid of the polypeptide chain.

The polypeptide is thus freed

from the ribosome.

When a ribosome reaches a stop

codon on mRNA, the A site of the

ribosome accepts a protein called

a release factor instead of tRNA.

The two ribosomal subunits

and the other components of

the assembly dissociate.

2

1

3

Termination of Translation
  • The final step in translation is termination. When the ribosome reaches a STOP codon, there is no corresponding transfer RNA.
  • Instead, a small protein called a “release factor” attaches to the stop codon.
  • The release factor causes the whole complex to fall apart: messenger RNA, the two ribosome subunits, the new polypeptide.
  • The messenger RNA can be translated many times, to produce many protein copies.
translation initiation
Translation: Initiation
  • mRNA binds to a ribosome, and the transfer RNA corresponding to the START codon binds to this complex. Ribosomes are composed of 2 subunits (large and small), which come together when the messenger RNA attaches during the initiation process.
translation elongation
Translation: Elongation
  • Elongation: the ribosome moves down the messenger RNA, adding new amino acids to the growing polypeptide chain.
  • The ribosome has 2 sites for binding transfer RNA. The first RNA with its attached amino acid binds to the first site, and then the transfer RNA corresponding to the second codon bind to the second site.
translation elongation36
Translation: Elongation
  • The ribosome then removes the amino acid from the first transfer RNA and attaches it to the second amino acid.
  • At this point, the first transfer RNA is empty: no attached amino acid, and the second transfer RNA has a chain of 2 amino acids attached to it.
translation termination
Translation: Termination
  • The elongation cycle repeats as the ribosome moves down the messenger RNA, translating it one codon and one amino acid at a time.
  • The process repeats until a STOP codon is reached.
polyribosomes

Completed

polypeptide

Growing

polypeptides

Incoming

ribosomal

subunits

Start of

mRNA

(5 end)

Polyribosome

End of

mRNA

(3 end)

An mRNA molecule is generally translated simultaneously

by several ribosomes in clusters called polyribosomes.

(a)

Ribosomes

mRNA

0.1 µm

This micrograph shows a large polyribosome in a prokaryotic

cell (TEM).

Polyribosomes
  • A number of ribosomes can translate a single mRNA molecule simultaneously forming a polyribosome
  • Polyribosomes enable a cell to make many copies of a polypeptide very quickly
comparing gene expression in prokaryotes and eukaryotes

RNA polymerase

DNA

mRNA

Polyribosome

Direction of

transcription

0.25 mm

RNA

polymerase

DNA

Polyribosome

Polypeptide

(amino end)

Ribosome

mRNA (5¢ end)

Comparing Gene Expression In Prokaryotes And Eukaryotes
  • In a eukaryotic cell:
    • The nuclear envelope separates transcription from translation
    • Extensive RNA processing occurs in the nucleus
  • Prokaryotic cells lack a nuclear envelope, allowing translation to begin while transcription progresses
a summary of transcription and translation in a eukaryotic cell

DNA

TRANSCRIPTION

1

3

4

2

5

RNA is transcribed

from a DNA template.

3

Poly-A

RNA

transcript

RNA

polymerase

5

Exon

RNA PROCESSING

In eukaryotes, the

RNA transcript (pre-

mRNA) is spliced and

modified to produce

mRNA, which moves

from the nucleus to the

cytoplasm.

RNA transcript

(pre-mRNA)

Intron

Aminoacyl-tRNA

synthetase

Cap

NUCLEUS

Amino

acid

FORMATION OF

INITIATION COMPLEX

AMINO ACID ACTIVATION

tRNA

CYTOPLASM

After leaving the

nucleus, mRNA attaches

to the ribosome.

Each amino acid

attaches to its proper tRNA

with the help of a specific

enzyme and ATP.

Growing

polypeptide

mRNA

Activated

amino acid

Poly-A

Poly-A

Ribosomal

subunits

Cap

5

TRANSLATION

C

C

A

U

A succession of tRNAs

add their amino acids to

the polypeptide chain

as the mRNA is moved

through the ribosome

one codon at a time.

(When completed, the

polypeptide is released

from the ribosome.)

A

E

A

C

Anticodon

A

A

A

U

G

U

G

G

U

U

U

A

Codon

Ribosome

A summary of transcription and translation in a eukaryotic cell

Figure 17.26

post translation
Post-translation
  • The new polypeptide is now floating loose in the cytoplasm if translated by a free ribosome.
  • Polypeptides fold spontaneously into their active configuration, and they spontaneously join with other polypeptides to form the final proteins.
  • Often translation is not sufficient to make a functional protein, polypeptide chains are modified after translation
  • Sometimes other molecules are also attached to the polypeptides: sugars, lipids, phosphates, etc. All of these have special purposes for protein function.
targeting polypeptides to specific locations
Targeting Polypeptides to Specific Locations
  • Completed proteins are targeted to specific sites in the cell
  • Two populations of ribosomes are evident in cells: free ribsomes (in the cytosol) and bound ribosomes (attached to the ER)
    • Free ribosomes mostly synthesize proteins that function in the cytosol
    • Bound ribosomes make proteins of the endomembrane system and proteins that are secreted from the cell
  • Ribosomes are identical and can switch from free to bound
targeting polypeptides to specific locations43

Ribosomes

mRNA

Signal

peptide

ER

membrane

Signal-

recognition

particle

(SRP)

Signal

peptide

removed

Protein

SRP

receptor

protein

CYTOSOL

Translocation

complex

ER LUMEN

Targeting Polypeptides to Specific Locations
  • Polypeptide synthesis always begins in the cytosol
  • Synthesis finishes in the cytosol unless the polypeptide signals the ribosome to attach to the ER
  • Polypeptides destined for the ER or for secretion are marked by a signal peptide
  • A signal-recognition particle (SRP) binds to the signal peptide
  • The SRP brings the signal peptide and its ribosome to the ER
mutation causes and rate
Mutation Causes and Rate
  • The natural replication of DNA produces occasional errors. DNA polymerase has an editing mechanism that decreases the rate, but it still exists
  • Typically genes incur base substitutions about once in every 10,000 to 1,000,000 cells
  • Since we have about 6 billion bases of DNA in each cell, virtually every cell in your body contains several mutations
  • Mutations can be harmful, lethal, helpful, silent
  • However, most mutations are neutral: have no effect
  • Only mutations in cells that become sperm or eggs—are passed on to future generations
  • Mutations in other body cells only cause trouble when they cause cancer or related diseases
mutagens
Mutagens
  • Mutagens are chemical or physical agents that interact with DNA to cause mutations.
  • Physical agents include high-energy radiation like X-rays and ultraviolet light
  • Chemical mutagens fall into several categories.
    • Chemicals that are base analogues that may be substituted into DNA, but they pair incorrectly during DNA replication.
    • Interference with DNA replication by inserting into DNA and distorting the double helix.
    • Chemical changes in bases that change their pairing properties.
  • Tests are often used as a preliminary screen of chemicals to identify those that may cause cancer
  • Most carcinogens are mutagenic and most mutagens are carcinogenic.
viral mutagens
Viral Mutagens
  • Scientists have recognized a number of tumor viruses that cause cancer in various animals, including humans
  • About 15% of human cancers are caused by viral infections that disrupt normal control of cell division
  • All tumor viruses transform cells into cancer cells through the integration of viral nucleic acid into host cell DNA.
point mutations
Point mutations
  • Point mutations involve alterations in the structure or location of a single gene. Generally, only one or a few base pairs are involved.
  • Point mutations can signficantly affect protein structureandfunction
  • Point mutations may be caused by physical damage to the DNA from radiation or chemicals, or may occur spontaneously
  • Point mutations are often caused by mutagens
point mutation

Wild-type hemoglobin DNA

Mutant hemoglobin DNA

In the DNA, the

mutant template

strand has an A where

the wild-type template

has a T.

3

5

3

5

T

T

C

A

T

C

mRNA

mRNA

The mutant mRNA has

a U instead of an A in

one codon.

G

A

A

U

A

G

5

3

5

3

Normal hemoglobin

Sickle-cell hemoglobin

The mutant (sickle-cell)

hemoglobin has a valine

(Val) instead of a glutamic

acid (Glu).

Val

Glu

Point Mutation
  • The change of a single nucleotide in the DNA’s template strand leads to the production of an abnormal protein
types of point mutations
Types of Point Mutations
  • Point mutations within a gene can be divided into two general categories
    • Base-pair substitutions - is the replacement of one nucleotide and its partner with another pair of nucleotides
    • Base-pair insertions or deletions - are additions or losses of nucleotide pairs in a gene
base pair substitutions

Wild type

A

A

G

G

G

G

A

U

U

U

C

U

A

A

U

mRNA

5

3

Lys

Protein

Met

Phe

Gly

Stop

Amino end

Carboxyl end

Base-pair substitution

No effect on amino acid sequence

U instead of C

A

U

G

A

A

G

U

U

U

G

G

U

U

A

A

Lys

Met

Phe

Gly

Stop

Missense

A instead of G

A

A

U

G

A

A

G

U

U

U

A

G

U

U

A

Lys

Met

Phe

Ser

Stop

Nonsense

U instead of A

G

A

A

G

G

U

U

G

A

A

U

U

U

U

C

Met

Stop

Base-Pair Substitutions
  • Silent - changes a codon but codes for the same amino acid
  • Missense - substitutions that change a codon for one amino acid into a codon for a different amino acid
  • Nonsense -substitutions that change a codon for one amino acid into a stop codon
insertions and deletions

Wild type

A

A

A

G

G

G

A

G

U

U

U

U

C

U

A

mRNA

3

5

Gly

Met

Lys

Phe

Protein

Stop

Amino end

Carboxyl end

Base-pair insertion or deletion

Frameshift causing immediate nonsense

Extra U

A

G

A

A

G

U

U

U

U

U

G

G

C

U

A

Met

Stop

Frameshift causing

extensive missense

Missing

U

A

A

A

U

A

G

U

A

G

U

U

G

G

C

Met

Lys

Ala

Leu

Insertion or deletion of 3 nucleotides:

no frameshift but extra or missing amino acid

Missing

A

A

G

A

G

G

A

A

G

U

U

U

U

U

C

Met

Phe

Gly

Stop

Insertions and Deletions
  • Are additions or losses of nucleotide pairs in a gene
  • May produce frameshift mutations that will change the reading frame of the gene, and alter all codons downstream from the mutation.