DNA Mutation and Repair

Question 1

N-Terminus nonsense mutation

Answer 1

The very first amino acids translated are those at the N-terminus of the sequence. Therefore, a nonsense mutation there will terminate translation at its beginning and drastically truncate the protein. This presents the most extreme disruption to protein function.

Question 2

C-Terminus nonsense mutation

Answer 2

A C-terminal nonsense mutation would remove one amino acid at the very C-terminus of the protein, which could result in a minor alteration to protein function.

Question 3

Conservative Mutation

Answer 3

A conservative mutation results in a new amino acid with similar properties to the original amino acid which it replaced. This type of mutation likely will not disrupt protein folding, and so the majority of protein function is retained.

Question 4

Non Conservative Mutation

Answer 4

A missense mutation that results in a new amino acid with dissimilar properties to the original amino acid is a non-conservative mutation. The function of a protein is determined by the structure which it folds into, which in turn is determined by the structural properties conferred by each amino acid in its primary sequence. When amino acid characteristics are altered, protein folding is altered, which would likely disrupt protein function.

Question 5

Silent Mutation

Answer 5

A silent mutation results in no change to primary structure. Therefore, it confers no effect at all on protein function.

Question 6

A glycine is mutated to an alanine. What would this be classified as?

Answer 6

Conservative mutation

Question 7

In a nascent protein being translated, what is the first terminus to exit the ribosome?

Answer 7

N-terminus. The protein is translated from N to C. Remember the backbone N-C-C.

Question 8

Place the following in order of most disruptive to least: Conservative mutation Non-conservative mutation Silent mutation C-terminal nonsense mutation N-terminal nonsense mutation

Answer 8

N-terminal nonsense mutation Non-conservative mutation C-terminal nonsense mutation Conservative mutation Silent mutation

Question 9

What damage can UV radiation cause to DNA?

Answer 9

Pyrimidine dimers

Question 10

How are Pyrimidine dimers repaired

Answer 10

Nucleotide excision is the process by which pyrimidine dimers, caused by UV radiation, are excised from DNA and the DNA is subsequently repaired.

Question 11

How is damage caused by free radicals repaired?

Answer 11

Free radicals can cause damage to DNA, which can be repaired on the level of individual nucleotides. This occurs through a process known as base excision.

Question 12

How are errors in DNA polymerase repaired?

Answer 12

3-5 exonuclease activity by DNA polymerase. DNA polymerase is responsible for replicating DNA, but also repairing DNA through 3’-to-5’ proofreading activity when it accidentally inserts an incorrect nucleotide.

Question 13

What are the Stop codons?

Answer 13

TAA, TAG, TGA UAA, UAG, UGA

Question 14

What are transposons?

Answer 14

Transposons are generally non-coding sequences of DNA which, through enzymatic action, can jump from location to location within the genome. When this jumping activity occurs from one chromosome to another, the resulting transposition is simply transposon genetic material being added to another chromosome with no other genetic material being exchanged. Thus, transposition can be described as unidirectional.

Question 15

True or false: A normal human cell contains 23 pairs of chromosomes, while a trisomic cell contains 24 pairs.

Answer 15

This statement is false. A normal human cell does have 23 pairs of homologous chromosomes. A trisomic cell also has 23 homologous chromosomes pairs; however, one of those pairs has an extra chromosome copy.

Question 16

A scientist exposes a cell line to mutagens. He then observes their phenotype to determine if any changes to the cells’ genetic material have occurred. He notices no change to protein expression, activity, or localization. If mutagenesis occurs would DNA polymerase be able to repair it?

Answer 16

DNA polymerase only repairs spontaneous mutations during DNA replication. Other processes, such as nucleotide and base excision, are responsible for repairs following mutagen-induced mutations.

Question 17

A scientist exposes a cell line to mutagens. He then observes their phenotype to determine if any changes to the cells’ genetic material have occurred. He notices no change to protein expression, activity, or localization. What would be able to repair the mutagenesis if it occured?

Answer 17

Nucelotide and Base excision would be able to repair this

Question 18

True or false: The cell membrane receptor for insulin is still likely to bind its ligand after a conservative mutation alters an amino acid which codes for part of the insulin receptor’s active site.

Answer 18

This statement is true. Conservative and non-conservative mutations are two types of missense mutations – DNA mutations which alter the amino acid that a 3-letter sequence of DNA codes for. A conservative mutation is a missense mutation which results in the production of a new amino acid bearing similar properties to the original amino acid (e.g. valine to leucine). Non-conservative mutations are missense mutations which result in the production of a new amino acid bearing very different properties to the original amino acid (e.g. valine to aspartic acid). The active site of a protein receptor is highly specific to the charge distribution and shape of its corresponding ligand. Because the mutation to the insulin receptor is conservative, the shape of its active site is likely conserved, and thus its ability to bind to its ligand stays intact.

Question 19

A scientist exposes a cell line to mutagens. He then observes their phenotype to determine if any changes to the cells’ genetic material have occurred. He notices no change to protein expression, activity, or localization. What could explain these findings?

Answer 19

For protein expression, activity, and localization to remain unchanged, the only possibility is that no amino acids were mutagenized or only conservative mutations occurred. Silent mutations by definition do not change protein structure. Missense mutations, on the other hand, do not necessarily conserve protein structure and activity. However, if only conservative missense mutations occurred, then protein expression, activity, and localization could remain unchanged.

Question 20

A couple gives birth to a child who has monosomy of chromosome 22, as well as having some genetic material translocated from chromosome 3 to chromosome 4. How would this impact gene expression?

Answer 20

Monosomy is an abnormal condition where one chromosome (of a pair of homologous chromosomes) has gone missing. Having only one copy of chromosome 22, the child will likely express only half as much gene product. As for the genetic material which has undergone translocation, a chromosomal aberration resulting in the location of genes switching from one chromosome to another, the gene copy count remains the same. Therefore, expressivity of genes on chromosomes 3 and 4 will likely remain unaltered.

Question 21

True or false: If individual DNA bases become oxidized, the appropriate repair process to fix them will be base excision repair.

Answer 21

This statement is true. If DNA damage needs to be repaired on the level of individual nucleotides, then this occurs through a process known as base excision repair.

Question 22

Scientists create an inactive version of the allele coding for Green Fluorescent Protein (GFP). The inactive allele differs from the wild type allele by only one nucleotide base pair. Scientists obtained a colony of cells which only contained copies of the inactive variant. What methods could scientists could potentially use to create a cell, from their colony of cells, containing a copy of the wild type GFP allele.

Answer 22

DNA mutations can occur as a result of damage to the chemical structure of DNA by environmental agents such as ionizing radiation or UV light, free radical attack, or excessive heating. So you could titrate the cells with a free radical species, If the cells described in the passage are exposed to high energy emissions from radioisotopes (e.g. beta, alpha, or gamma emissions), then the DNA containing an inactive allele may undergo a substitution mutation . Or If the cells described in the passage are exposed to high energy ultraviolet light, then the DNA acted on by the UV rays will likely form pyrimidine dimers, which is not a sufficient condition to reverse a point mutation as described in the passage. However, radicalization of oxygen will create free radicals that can damage DNA and cause point mutations.

Question 23

How can you induce DNA mutations?

Answer 23

DNA mutations can occur as a result of damage to the chemical structure of DNA by environmental agents such as ionizing radiation or UV light, free radical attack, or excessive heating.

Question 24

Mutagen induced vs spontaneous DNA mutations

Answer 24

Mutagens are generally environmental agents that can damage our DNA and induce mutations. For example, exposing a person to UV light will induce DNA mutations. However, there is no reason to believe that a person is exposed to more mutagens as they age. However, spontaneous DNA mutations are mutations that result from natural biological processes such as errors in DNA repair. Spontaneous mutations increase as we age, because errors in processes such as DNA repair increase as we age.

Question 25

True or false: The negative side effects of aging are, in part, likely due to an increase in the rate of mutagen-induced DNA mutations.

Answer 25

This statement is false. It is true that an increase in the rate of DNA mutations as we age is thought to be one of the primary factors related to the negative side effects of aging. However, this question relies on an understanding of the difference between mutagen-induced and spontaneous DNA mutations.

Question 26

What levels of cell functionality may be impacted by as a result of a mutation in DNA?

Answer 26

Gene expression, protein translation, protein product secretion, intracellular cargo trafficking

Question 27

True or false: A receptor tyrosine kinase (RTK) initially has the capability to bind to its ligand, insulin. However, after a substitution mutation, the RTK’s active site is able to bind to insulin-like growth factor (IGF). This mutation must have been a gain-of-function mutation.

Answer 27

This statement is true. Because the RTK protein receptor, located in the membrane of a cell, gains the ability to bind to a second ligand, it must have undergone a gain-of-function mutation. The definition of a gain-of-function mutation is any mutation which causes a protein to have new or enhanced functionality. The definition of a loss-of-function mutation is any mutation which causes a protein to have reduced functionality.

Question 28

Scientists discover a new gene on chromosome 12. At least one copy of the wild-type allele is required for hair production. Increased expressivity of the gene is shown to be correlated with increased hair growth. Later, scientists discover a man, who has monosomy of chromosome 12, and a woman, whose chromosome 12 has undergone translocation. Based on this information, what is a likely outcome?

Answer 28

Monosomy is an abnormal condition where one chromosome (of a pair of homologous chromosomes) has gone missing. Having only one copy of chromosome 12, the man will likely express only half as much gene product, reducing his potential for hair growth. The woman has undergone translocation, a chromosomal aberration causing the location of genes on a chromosome to become altered. This does not increase or decrease gene copy count, and therefore will not be likely to impact the levels of gene expression in the woman.

Question 29

Aneuploidy

Answer 29

Aneuploidy is a broad term which describes occurrences where a person’s chromosome number is abnormal. There are specific terms to describe instances where people have a specified abnormal number of chromosomes – for example, a person missing one copy of a pair of homologous chromosomes is displaying monosomy, while having an extra chromosome is trisomy. Chromosome count abnormalities can be caused by nondisjunction errors during meiosis. During meiosis II, for example, if nondisjunction occurs between homologous chromosomes, then one of the resulting gametes will have an extra copy of the chromosome, while another gamete will have one less copy.

Question 30

What is occuring in the figure?

Answer 30

Nondysjunction

Question 31

What happens in nondisjunction?

Answer 31

nondisjunction occurs between homologous chromosomes- one of the resulting gametes will have an extra copy of the chromosome, while another gamete will have one less copy. Division of homologous chromosomes is incorrect.

Question 32

For which of the following cell types will a translocation in a parent potentially alter levels of gene expression in either that parent or the parent’s offspring?

Answer 32

A spermatagonium is the diploid precursor to haploid spermatids. In other words, spermatagonia undergo meiotic divisions to form haploid gametes, eventually divvying up their genetic material between 4 daughter gametes. If a translocation occurs in a spermatagonium and one chromosome ends up with one extra gene copy, while another chromosome ends up with one less, the resultant daughter gametes could eventually produce offspring with extra or fewer copies of genetic material. Offspring with extra or fewer copies of genes on their chromosomes may have altered gene expression, producing more or less mRNA, respectively. It owuld not happen in spermatids because they are haploid.

Question 33

True or false: Transposition occurs when genetic material is unidirectionally exchanged between two chromosomes as a result of the activity of transposons.

Answer 33

This statement is true. Transposons are generally non-coding sequences of DNA which, through enzymatic action, can jump from location to location within the genome. When this jumping activity occurs from one chromosome to another, the resulting transposition is simply transposon genetic material being added to another chromosome with no other genetic material being exchanged. Thus, transposition can be described as unidirectional.

Question 34

Which strand of DNA in replication will be more methylated, older or newer strand?

Answer 34

DNA methylation does inform DNA polymerase which strand is which. However, methylation of DNA occurs naturally over time, and so the older DNA strand will be more highly methylated than the newer one.

Question 35

A cell’s DNA was mutagenized by light with a wavelength lower than those of the visible spectrum, but was then successively repaired. What describes the repair process used by the cell to repair the damaged section of DNA? (Note that the λ of blue light is approximately 350 nm, and the λ of red light is approximately 700 nm.)

Answer 35

Dimerized cytosines were excised and repaired

Question 36

A student accidently spills peroxide on a cell culture. What could happen?

Answer 36

Peroxide is a reactive oxygen species, a class of chemicals which contains oxygen and generates highly reactive free radicals. As such, peroxide is likely to damage DNA and one could reasonably predict that it induced base excision repair.

Question 37

True or false: Base mismatch errors made during transcription, which do not get noticed by proofreading enzymes, are the primary source of spontaneous changes to the genetic code.

Answer 37

This statement is false. Base mismatch errors during TRANSCRIPTION would lead to an incorrect mRNA transcript. A strand of mRNA exists only transiently, coding for its respective protein, before degrading. Unnoticed base mismatching during REPLICATION will cause permanent changes to the genetic code in a cell, irreversibly altering a cell’s DNA.

Question 38

True or false: A mutagen is any physical or chemical agent from outside the body which increases the observed frequency of DNA mutations.

Answer 38

The statement is false. While mutagens do increase the frequency of DNA mutations, they do not necessarily have to be from outside the body.

Question 39

True or false: Both aneuploidy and chromosomal deletions can reduce gene expressivity.

Answer 39

This statement is true. Relative transcription of genes is limited by the number of copies of each gene. Aneuploidy is an abnormal number of chromosomes, an example of which is monosomy, or the deletion of an entire chromosome. Chromosomal deletions result in the loss of regions of genetic material along a chromosome. Therefore, both are likely to reduce gene copy number and reduce gene expressivity.