Unit 3 (Week 11 Mutations DNA Repair and Cancer) Flashcards
The children at this camp have inherited a disorder called xeroderma pigmentosum (XP), which makes them highly sensitive to sunlight. Their skin will blister or freckle on minimum exposure to sunlight. Of greater concern, however, is skin cancer.
What explains the symptoms of XP?
Individuals with this condition are highly susceptible to mutation, which is defined as a heritable change in the genetic material.
Should we be afraid of mutations?
Yes and no. On the positive side, mutations are essential to the long-term continuity of life. Mutations provide the foundation for evolutionary change. They supply the variation that enables species to evolve and become better adapted to their environments. On the negative side, however, new mutations are more likely to be harmful than beneficial to the individual. The genes within modern species are the products of billions of years of evolution and have evolved to work properly. Random mutations are more likely to disrupt genes rather than enhance their function.
A mutation is best defined as ______.
Multiple choice question.
a heritable change in the genetic material
an exchange of genetic material between two individuals
a permanent change in protein structure
a heritable change in the genetic material
Mutations are essential for the long-term continuity of life because they supply the _______________-
variation that is the foundation for evolutionary change.
genetic, gene, genomic, DNA, heritable, enabling, allelic, allele, or essential
Relatively small changes in DNA sequence are known as:
Multiple choice question.
nucleotides
splice junctions
transposable elements
gene mutations
mutagens
gene mutations
What are gene mutations?
Relatively small changes in the sequence of bases in a particular gene.
What are the two basic types of changes to a gene? (2)
- Base sequence within a gene can be changed
2. One or more base pairs can be added to or removed from a gene.
What is a mutation that affects only a single base pair within DNA or that involves the addition or deletion of a single base pair to a DNA sequence?
Point mutation
What is a mutation that involves the substitution of a single base in the DNA for another base?
Base substitution
Where must a mutation occur that can alter the sequence in a variety of ways?
The coding region of a protein-encoding gene.
What is a gene mutation that does not alter the amino acid sequence of the polypeptide, even though the base sequence has changed?
Silent mutation
Remember: Genetic code is degenerate meaning that one codon can specify the same amino acid. These mutations happen normally in the third base.
What is a base substitution that changes a single amino acid in a polypeptide?
Missense mutation.
Why might a missense mutation not alter protein function?
It changes only a single amino acid within a polypeptide that is typically hundreds of amino acids in length. A missense mutation that substitutes an amino acid with a chemistry similar to the original amino acid is less likely to alter protein function.
Example: Missense mutation that substitutes a glutamic acid for an aspartic acid may not alter protein function because both amino acids are negatively charged and have similar side chain structures.
What disease is an example of a striking change when a missense mutation occurs?
Sickle cell disease.
This is a disease due to a mutation in a hemoglobin gene that results in sickle-shaped red blood cells that are less able to move smoothly through capillaries and can block blood flow, resulting in pain and cell death of the surrounding tissue.
What gene specifically is affected in sickle cell disease?
Missense mutation of the B-globin gene.
The 6th amino acid is changed from a glutamic acid to valine. The striking difference between these two amino acids is one is hydrophilic while the other is hydrophobic, changing the structure of the cell.
Based on the fiber-like structures seen in part (c) of this figure, what aspect of hemoglobin structure does a glutamic acid at the sixth position in normal β-globin prevent? Speculate as to how the charge of this amino acid may play a role.
At neutral pH, glutamic acid is negatively charged. Perhaps the negative charges repel each other and prevent hemoglobin proteins from aggregating into fiber-like structures.
What is a mutation that changes a normal codon into a stop codon; this causes translation to be terminated earlier than expected, producing a truncated polypeptide?
Nonsense mutation
What is a mutation that involves the addition or deletion of a number of nucleotides that is not a multiple of three and alters the reading frame of a protein-encoding gene?
Frameshift mutation
T/F A mutation can occur within a noncoding DNA sequence and affect gene expression.
True
Ex. The promoter region with a mutation may increase or decrease the rate of transcription.
What can happen if there is a mutation in the regulatory elements or operator site in the context of the lac operon?
Regulatory elements such as the lac operator site in E. coli, which is recognized by the lac repressor, can disrupt the proper regulation of the lac operon. The lac repressor would not bind to the lac operator site causing the operon to constitutively be expressed and waste energy and resources within the cell.
What are the two types of cells that geneticists classify cells as?
Germ-line cells & somatic cells.
What are the cells that give rise to gametes, such as an egg and sperm cells?
Germ line
A germ-line mutation can occur directly in an egg or sperm cell, or it can occur in a precursor cell that produces the gamete.
What constitutes for all cells within the body of an animal or plant except those that give rise to gametes?
Somatic cells.
Example is skin and muscle cells. The larger the affected area, the earlier the mutation happened after the embryo was created.
What do you call an individual with somatic regions that are genetically different from each other?
Mosaic.
Ex. A child with a grey streak of hair. This is due to a somatic mutation in a single cell during embryonic development. This cell continued to divide to produce a streak of white hair. This also creates a mosaic.
Can this child with a streak of white hair transmit this trait to his future offspring?
This trait is due to a mutation that occurred in a somatic cell, so it cannot be transmitted to the individual’s offspring.
How do point mutations affect DNA sequences? Choose all that apply.
Multiple select question.
by adding or subtracting a single base pair
by rearrangement of nucleotides
by inserting a sequence of multiple base pairs into the existing DNA molecule
by substituting one base for another
by reinserting a portion of the sequence in reverse order
by adding or subtracting a single base pair
by substituting one base for another
What is a point mutation?
Multiple choice question.
A mutation that occurs in a somatic cell
A mutation that occurs at a particular developmental stage
A mutation that changes a normal codon to a stop codon
A mutation that affects only a single base pair
A mutation that is induced by an environmental agent
A mutation that affects only a single base pair
A heritable change in genetic material is known as a(n) _________.
Mutation
Consider the following wild-type DNA sequence: 5’-CCAAGGTT-3’. Which of the following mutations is a base substitution?
Multiple choice question.
5’-CCCAAGGTT-3’
5’-CCAGGTT-3’
5’-CCCAGGTT-3’
5’-CCCAGGTT-3’
True or false: New mutations are much more likely to be harmful than beneficial to the individual.
True false question.
True
False
True
A point mutation in which one base pair is replaced by another is known as a(n) base ______
Substitution
What does a gene mutation affect?
Multiple choice question.
The total number of chromosomes
The overall structure of one or more chromosomes
The sequence of bases in a particular gene
The sequence of bases in a particular gene
Where must a mutation occur if it is to directly affect an amino acid sequence?
Multiple choice question.
The promoter of a gene
The intergenic region
Transcriptional regulatory elements
An operator site
The coding region of a structural gene
The coding region of a structural gene
Select all that apply
Which of the following are ways that point mutations may alter a gene?
Multiple select question.
A nucleotide is removed from a gene.
The base sequence within the gene is changed.
The total chromosome number is changed.
A nucleotide is added to a gene.
A nucleotide is removed from a gene.
The base sequence within the gene is changed.
A nucleotide is added to a gene.
Place the following types of mutations in order from the least effect on polypeptide sequence at the top to the most dramatic effect on polypeptide sequence at the bottom.
Missense, Nonsense, and Silent
Silent, Missense, Nonsense
True or false: Nonsense and frameshift mutations generally result in less dramatic changes to a polypeptide sequence than missense mutations.
False
Reason: In general, nonsense and frameshift mutations have a much larger effect on protein structure and function than missense mutations. This is because missense mutations only affect a single amino acid, whereas nonsense and frameshift mutations have the potential to affect many more.
Gametes are produced by ______.
Multiple choice question.
all organisms
all human cells
germ-line cells
somatic cells
germ-line cells
Silent mutations have no effect on the amino acid sequence of a polypeptide because ______.
Multiple choice question.
the base substitution results in a codon that specifies the same amino acid as the original sequence
mRNA does not recognize the base substitution, so the same polypeptide is produced during translation
the mutation changes only a single amino acid in the polypeptide sequence
although a base substitution occurs, the nucleotide excision repair system restores it to the original
the base substitution results in a codon that specifies the same amino acid as the original sequence
How did the Lederberg’s start the experiment?
They placed a few dozen E. coli bacteria onto growth media and incubated them overnight. Following this growth period, each bacterial cell had divided many times to form a visible bacterial colony composed of millions of cells. This is called the master plate.
What technique did the Lederberg’s use?
Replica plating, which is a technique in which a replica of bacterial colonies is transferred from one petri plate to a new petri plate.
In the Lederberg experiment, they transferred this replica to two secondary colonies containing an agent that selected for the growth of bacterial cells with a particular mutation.
What was the final steps of the Lederberg experiment?
They placed the bacterial colonies on the TI bacteriophages which cause the E. coli to lyse. Incubating overnight, some cells lysed and others defended against the TI bacteriophages. This solidified the understanding that mutations were random because these mutations occurred before placement with T1.
Explain the opposing views of mutation prior to the Lederbergs’ study.
Some biologists believed that heritable traits may be altered by physiological events. This view suggests that mutations may be stimulated by certain needs of the organism. Others believed that mutations are random. If a mutation had a beneficial effect that improved survival and/or reproductive success, it would be more likely to be maintained in the population through natural selection.
What hypothesis was being tested by the Lederbergs?
The Lederbergs were testing the hypothesis that mutations are random events.
How did the results of the Lederbergs support or falsify the hypothesis?
When the researchers looked at the locations on the secondary plates of colonies that were resistant to the bacteriophages, the pattern was the same on the two plates. This indicates that the mutation that allowed the colonies to be resistant to the virus occurred on the master plate. Thus, the mutation occurred randomly and was not caused by exposure to the virus.
How do biologists categorize mutations?
As spontaneous and induced.
What is a mutation resulting from some abnormality in a biological process?
Spontaneous mutation.
Spontaneous mutations reflect the observation that biology isn’t perfect. Enzymes, for example, can function abnormally.
In addition, normal metabolic processes within the cell may produce toxic chemicals such as free radicals that can react directly with the DNA and alter its structure. Finally, the structures of nucleotides are not absolutely stable. On occasion, the structure of a base may spontaneously change, and such a change may cause a mutation if it occurs immediately prior to DNA replication.
T/F Smaller genes are usually more likely to incur a mutation than smaller ones.
False. Larger genes are more likely to incur a mutation.
What is the common rate of mutation among various species?
1 mutation for every 1 million genes per cell division, which equals 1 in 10^6, or simply 10^-6.
This is the expected rate of spontaneous mutation, which CREATES the variation that is raw material of evolution.
What is a mutation brought about by environmental agents that enter the cell and then alter the structure of DNA?
Induced mutation.
T/F Mutation rate in induced mutation is higher than spontaneous mutant rates.
True. These are caused by mutagens, agents that cause mutation.
How are mutagenic agents are categorized how?
Chemical and physical mutagens.
[Focus Common Causes of Spontaneous and Induced Mutations]
What are some common causes of spontaneous mutations and what are their description? (4)
What are some common causes of induced mutations and what are their description? (4)
Spontaneous mutations:
Errors in DNA replication - A mistake by DNA polymerase may cause a point mutation
Toxic metabolic products - The products of normal metabolic processes may be reactive chemicals such as free radicals that can alter the structure of DNA.
Changes in nucleotide structure - On rare occasions, the linkage between a purine and deoxyribose can spontaneously break. Changes in base structure (isomerization) may cause mispairing during DNA replication.
Transposons - Transposons are small segments of DNA that can insert at various sites in the genome. If they insert into a gene, they may inactivate the gene.
Induced Mutations:
Chemical agents - Chemical substances, such as benzo(a)pyrene, a chemical found in cigarette smoke, may cause changes in the structure of DNA.
Physical agents - Physical agents such as UV (ultraviolet) light and X-rays can damage DNA.
What chemical mutagen deanimates bases by replacing amino groups with keto groups which changes cytosine to uracil?
Nitrous Acid (HNO2)
What are base analogues?
They have structures that are similar to particular bases in DNA and can substitute them but cause errors in DNA replication.
What type of radiation has short wavelengths and high energy is known to alter DNA structure? This includes X-rays and gamma rays.
Ionizing radiation.
This type of radiation can penetrate deeply into biological materials, where it creates free radicals.
Nonionizing radiation, such as UV light, contains less energy, and so it penetrates only the surface of biological materials, such as the skin. Nevertheless, UV light is known to cause mutations. For example, UV light can cause the formation of a thymine dimer, which is a site where two adjacent thymine bases become covalently crosslinked to each other
What is a test that helps ascertain whether or not an agent is a mutagen by using a strain of a bacterium, Salmonella typhimurium?
Ames test
This Salmonella typhimurium cannot synthesis the amino acid, histidine because of a point mutation.
What does the Ames test actually measure?
With the Salmonella bacteria with a mutation that renders it unable to synthesize histidine, the test measures the time that a possible mutagenic agent mutates the strain again to allow it to correct the first in a way that allows the salmonella to synthesize histidine.
Note: Biologists have developed many methods, including the Ames test, for determining if a substance is a mutagen. The results of these tests have prevented the use of many different chemicals in the production of food and also resulted in warning labels on products such as cigarettes.
Interestingly, many studies have used the Ames test to compare the urine from cigarette smokers with that from nonsmokers. This research has shown that urine from smokers contains much higher levels of mutagens.
None
What is the process in which bacterial colonies are transferred from a master plate to secondary plates in the same configuration using a transferring agent such as a sterile velvet cloth?
Multiple choice question.
replica plating
secondary plating
T1 bacteriophage transfer
velvet transfer
replica plating
What is an example of how mutations in an operator site alter regulation of gene transcription?
Multiple choice question.
A change in nucleotide sequence, but no change in protein structure or function.
A change in amino acid sequence so that the structure and function of the hemoglobin protein are altered.
A change of a DNA sequence in E. coli so that the lac repressor protein no longer binds to it.
A change of a DNA sequence in E. coli so that the lac repressor protein no longer binds to it.
Mutations can be divided into two main types. Spontaneous mutations result from abnormalities in biological processes, while those that are caused by environmental agents that enter the cell and alter the structure of DNA are called _________ mutations.
Induced
Which of the following are examples of ionizing radiation?
Multiple select question.
UV light
Visible light
X-rays
Gamma rays
X-rays
Gamma rays
Select all that apply
Animal cells are classified into two main types. Which ones?
Multiple select question.
Adult cells
Stem cells
Embryonic cells
Non-stem cells
Somatic cells
Germ-line cells
Somatic cells
Germ-line cells
Ultraviolet light can cause the formation of a(n) _______ __________ in DNA.
Thymine dimer
n what types of cells do germ-line mutations occur?
Multiple select question.
Egg
Skin
Brain
Sperm
Skeletal muscle
Gamete-producing precursors
Egg
Sperm
Gamete-producing precursors
Induced mutations are caused by ______.
Multiple choice question.
errors in DNA replication
toxic metabolic products produced by cellular metabolism
environmental agents
spontaneous changes in nucleotide structure
transposon insertions within genes
Environmental agents
True or false: All living things possess mechanisms allowing them to minimize mutation.
True false question.
True
False
True
X-rays and gamma rays are examples of __________
radiation, which is a type of electromagnetic radiation that can create free radicals.
Ionizing
T/F Mutations are random events that often have negative consequences and all living things have the ability to repair changes that occur in the structure of DNA.
True
How do organisms minimize the occurrence of mutations?
Cells contain several DNA repair systems that can fix different types of DNA alterations. Each repair system is composed of one or more proteins that play specific roles in the repair mechanism. DNA repair requires two coordinated events.
What are the two coordinated events in the repair systems?
- One or more proteins in the repair system detect an irregularity in DNA structure.
- Abnormality is repaired.
What is an example of a change in DNA being directly repaired?
An alkyl group, -CH2CH3, can be added to a base.
For DIRECT REPAIR, an enzyme removes this alkyl group, thereby restoring the structure of the original base.
In most cases, the altered DNA is actually removed, and a new segment is synthesized.
What system is an important mechanism of DNA repair that is not related to direct repair?
The nucleotide excision repair (NER) system.
What is the third repair system that is not direct or NER?
Methyl-directed mismatch repair.
Similar to excision repair except that the DNA defect is a base pair mismatch in the DNA, not an abnormal nucleotide. The mismatch is recognized, and a strand of DNA in this region is removed. The complementary strand is used to synthesize a normal strand of DNA.
Explain NER.
- A region encompassing several nucleotides in the damaged strand is removed from the DNA
- The intact undamaged strand is used as a template for the resynthesis of a normal complementary strand.
- NER can fix many different types of DNA damage, including UV-induced damage, chemically modified bases, missing bases, and various types of crosslinks (such as thymine dimers). The system is found in all species, although its molecular mechanism is best understood in bacteria.
What are the four key proteins in NER system and why are they named the way they are?
UvrA, UvrB, UvrC, and UvrD.
They are named Uvr because they are involved in ultraviolet light repair of thymine dimers, although these proteins are also important in repairing chemically damaged DNA. In addition, DNA polymerase and DNA ligase are required to complete the repair process.
Explain, in detail, how the NER system works.
- Two UvrA proteins and one UvrB protein form a complex that tracks along the DNA (Figure 15.8). Damaged DNA will have a distorted double helix, which is sensed by the UvrA-UvrB complex.
- When the complex identifies a damaged site, the two UvrA proteins are released, and UvrC binds to UvrB at the site.
- The UvrC protein makes incisions in one DNA strand on both sides of the damaged site.
- After this incision process, UvrC is released. UvrD binds to UvrB. UvrD then begins to separate the DNA strands, and UvrB is released. The action of UvrD unravels the DNA, which removes a short DNA strand that contains the damaged region. UvrD is released.
- After the damaged DNA strand is removed, a gap is left in the double helix. DNA polymerase fills in the gap using the undamaged strand as a template. Finally, DNA ligase makes the final covalent connection between the newly made DNA and the original DNA strand.
