BSC 120 CHAPTER 14
The following sequence of DNA is the normal, wild-type gene. 5' ATG C(G)G GTA GTT AGC CGA TAG 3' An insertion occurs during DNA replication, causing an additional GUANINE to be inserted into the nucleotide strand after the GUANINE shown in red. What effect will this have on the final protein?
The addition of the G will not have an effect on the final protein. The addition of the G will cause a frame shift, so that the first amino acid after the mutation will change. The addition of the G will cause a frame shift, resulting in a premature stop codon and a truncated protein. The addition of the G will cause a single amino acid substitution in the codon in which it occurs.
A chromosome has undergone a translocation mutation that has completely deleted its centromere region, preventing association with spindle fibers. What will be the fate of this cell?
The cell will not pass this M phase checkpoint because its chromosomes will not all associate with spindle fibers. The cell will not pass the G1 checkpoint. It will survive for a time, and then die. The cell will not pass the G2 checkpoint because its DNA will not replicate properly. The cell will not pass the G1 checkpoint. It will immediately be killed by apoptosis.
A mutation has occurred that prevents UvrA and UvrB from forming a complex. What result will this have on damaged DNA?
The damaged segment of DNA will be recognized and cut, but it will not be separated from the healthy strand. The damaged DNA will be recognized, but no cut will be made to the damaged segment. The damaged DNA will not be recognized. The damaged segment of DNA will be removed from the DNA and replaced with the proper nucleotides, but there will be a nick in the nucleotide strand that will not be sealed.
A mutation has occurred that has made UvrD non-Functional. What result will this have on damaged DNA?
The damaged segment of DNA will be recognized and cut, but it will not be separated from the healthy strand. The damaged segment of DNA will be recognized and removed from the DNA, but new nucleotides will not replace those that were removed. The damaged DNA will not be recognized. The damaged segment of DNA will be removed from the DNA and replaced with the proper nucleotides, but there will be a nick in the nucleotide strand that will not be sealed.
An actively dividing cell is missing an entire chromosome. How might this lead to cancer
The deleted chromosome will signal certain genes, like p53, to promote apoptosis. Various proto-oncogenes may have been deleted from the genome, so cells will not divide when they should. Various tumor suppressor genes may have been deleted from the genome, so cell proliferation occurs regardless of the damaged genome. The proto-oncogene ras will lose its ability to hydrolyze GTP to form GDP. It will continue to promote cell division and lead to cancer.
The following sequence of DNA is part of the normal, wild-type gene. 5' ATG C(G)G GTA GTT AGC CGA TAG 3' A deletion occurs during DNA replication, causing the guanine shown in red to be removed from the nucleotide strand. What effect is this most likely to have on the final protein?
The deletion of the G will not have an effect on the final protein. The deletion of the G will cause a frame shift, so that the first amino acid after the mutation will change. The deletion of the G will cause a frame shift, resulting in a premature stop codon and a truncated protein. The deletion of the G will cause a single amino acid substitution in the codon in which it occurs.
Which of the following mutations might result in the formation of an oncogene?
The duplication of a proto-oncogene, so that it occurs several times in a single chromosome The deletion of a chromosome containing a proto-oncogene Methylation of a proto-oncogene A mutation in the repressor of a proto-oncogene, causing the repressor to stay permanently bound to the promoter
Insert the correct terms in the following statements about oncogenes, tumor suppressor genes, and mutations involved in cancer. missense mutation virus nonsense mutation cell division intron cell death deletion chromosomal translocation copies checkpoint
The insertion of a ____________ into the promoter of a gene could result in increased expression of the gene, resulting in cancer. A ____________ can cause fusion of two genes together, resulting in formation of a chimeric oncogene. A change in the number of COPIESof a gene can cause too much protein to be made. A ____________ can alter the structure of a protein (but not the total number of amino acids) so that it now has abnormally high activity. Many cells that have accumulated mutations are eliminated by CELL DEATH. If a cell accumulates DNA damage during mitosis, the cell cycle can pause at a CHECKPOINT . .
Evaluate the following statements and determine which is the most likely explanatin for how the methylation of a guanine might induce mutations in the DNA
The methyl group will cause the guanine to hydrogen bond with another guanine across the double helix. The guanine will be excised without being repaired, causing a deletion. The guanine will not properly hydrogen bond with cytosine across the double helix.
A pregnant mother recently had an ultrasound that indicated massive defects in the formation of her unborn baby's heart. Other oddities were noted in the spinal cord region, the kidneys, and the formation of the facial features. She had an amniocentesis to examine the baby's karyotype, and it was noted that there was a deletion of a small piece of one chromosome. The doctors advised her that her that she would likely miscarry. The devastated parents consult you as a genetic advisor on the likelihood that a future pregnancy would end similarly. What advice do you give this couple?
The mutation was probably a germ-line mutation that only affected a single egg or sperm, so they should try to have more children.
Many genes that are associated with cancer can become mutated due to slipped-strand mispairing. These genes include p53, retinoblastoma, Wilms tumor, and the breast cancer gene BRCA1. What characteristic would you expect to find in all these genes?
They are all susceptible to tautomeric shifts. They all have repetitive sequences in the gene. They are all easily mutated by virus. They all have regions that are susceptible to thymine dimers.
The growth factors illustrated in this system are positive regulatory growth factors. Why are they considered 'positive' growth factors?
They decrease the rate of cell proliferation. They prevent cancerous growth. They are always expressed by healthy cells. They increase the rate of cell proliferation.
How does ultraviolet light result in the formation of thymine dimers?
Ultraviolet light causes breaks in the double helix. Thymine dimers form as a 'quick fix' for the damaged DNA. Ultraviolet light causes one thymine to become ionized. It will then form a bond with the adjacent thymine. Ultraviolet light provides the energy for covalent bond formation between two thymines.
Which of the following synthesizes the new DNA strand?
UvrA-UvrB trimer DNA ligase DNA polymerase
Which protein cuts the damaged DNA strand?
UvrC UvrA UvrB
Which protein has a helicase function?
UvrC UvrD UvrA
After a tautomeric shift in adenine
adenine bonds with cytosine. adenine bonds with thymine. adenine is unable to bond with any molecule.
A eukaryotic cell that receives a "go-ahead" signal at the G1 checkpoint of the cell cycle will
complete the cycle and divide. move directly into the G2 phase. enter a resting stage. stop growing.
How does UV light and other ionizing radiation damage DNA molecules?
creating adenine dimers between adjacent adenines in the DNA chain. all of these are possible creating thymine dimers between adjacent thymines in the DNA chain. creating guanine dimers between adjacent guanines in the DNA chain.
Mutated forms of the Rb protein
do not bind to E2F thereby inhibiting cell division. bind to E2F but have no effect on cell division. do not bind to E2F thereby promoting uncontrolled cell division. bind to E2F thereby inhibiting cell division.
Oncogenes and tumor-suppressor genes have the shared property that
either type of gene encodes a protein with a kinase domain. both types are involved in DNA replication. when either type of gene is mutated, cancer can result. viruses can carry either type of gene, causing cancer in infected cells.
When a tautomeric shift occurs, the resulting nucleotide is a(n) __________________ of the nucleotide prior to the shift.
geometric isomer ion isotope structural isomer
In a tautomeric shift
hydrogen atoms move to form a nucleotide base with altered bonding properties.
Slipped-strand mispairing requires that a DNA sequence be present
in two copies on a homologous chromosome but no copies in the other. in only a single copy on both homologous chromosomes. in multiple copies on both homologous chromosomes. in multiple copies on a homologous chromosome but no copies in the other.
The mutations observed by the Lederbergs were
induced by x-ray radiation. induced by benzopyrene. spontaneous. induced by UV radiation.
The success of DNA replication is assessed during the ______ phase.
m s c g2
The nucleic acid sequence in mRNA is determined by
nucleotide sequence in DNA.
A mutation in a gene in the fruit fly Drosophila was found to affect eye color. The protein affected was found to be completely normal in its molecular weight and amino acid sequence, although much less of the protein is made in mutant flies. A reasonable explanation for the change in levels of protein is that the mutation
occurs in the promoter of the gene, within several hundred base pairs of the start of transcription. affects the splicing of the mRNA. causes the stop codon to be replaced by a sense codon. is a frame shift mutation near the start of the coding region.
The protein ________ checks for damaged DNA, thereby acting as a "quality control" for the cell.
p53
The proteins ________ work together to free the transcription factor that is bound by the retinoblastoma protein.
p53 and cyclin cyclin and E2F cyclin and cyclin dependent kinase p53 and p21
During slipped-strand mispairing, homologous chromosomes
pair up with each other, but then they are both degraded. pair up with each other, but out of register. pair up with different homologous chromosome pairs. do not pair up with each other.
If the protein retinoblastoma is ________, it can bind to and ________ the Myc protein.
phosphorylated ; inactivate phosphorylated ; activate either phosphorylated ; inactivate or dephosphorylated ; activate dephosphorylated ; inactivate
A tumor suppressor gene normally functions to
prevent development of cancer. mutate DNA in non-dividing cells. cause growth of tumors from non-tumor cells. increase damage to DNA resulting from UV light.
What kind of bond do thymine dimers weaken?
sulfide bonds all of these choices. hydrogen bonds. ionic bonds
In light repair
the damaged segment of DNA is excised by DNA ligase. a single thymine is excised. the covalent bonds between the thymine dimers are broken.
If a frameshift mutation causes a stop codon to be inserted into the DNA sequence,
the resulting protein will be too long and non-functional. the phenotype will change but not the genotype. the resulting protein will be too short and non-functional.
Slipped-strand mispairing may cause deletions resulting in
transposition. a frameshift mutation. inhibition of translation. a single base substitution.
A gene encodes a protein that normally functions in promoting the programmed cell death of blood cells that have accumulated damage to DNA. A mutation in this gene can result in leukemia (cancer of the blood). This gene is an example of a/an
tumor-suppressor gene.
The Ras protein normally regulates cell growth. A mutation that occurs in the gene encoding Ras can cause Ras to become overactive, which results in cancer. This means that Ras is an example of a/an
tumor-suppressor gene. proto-oncogene. retrovirus. carcinogen.
For each of the following examples of mutations in the codon sequences of a gene, predict the likely effect on the function of the polypeptide gene product (no effect on function, weak effect, or strong effect). You will need to consult the genetic code in Table 12.1. Note that the codons shown in the examples correspond to the coding strand of the DNA—recall how the sequence of the coding strand relates to the mRNA. STRONG EFFECT NO EFFECT WEAK EFFECT
-GAG-->GTG change in important part of the coding region NOT NO -CGA -->TGA near beginning of gene NOT WEAK -AAG-->AAA in middle of gene NOT WEAK -change of a codon for one acidic amino acid into another acidic amino acid NOT STRONG -insertion of one base (+1) shortly after start codon NOT WEAK -TGA -->TAA at end of coding region NOT WEAK -change of a C to a G before the ATG NO EFFECT .
A cell has a mutation such that UvrA is permanently attached to UvrB. What effect might this have on nucleotide excision repair (NER)?
-The cell would be able to recognize damaged regions of the double helix, but it would be unable cut the DNA in the appropriate region in preparation for removing the damaged sequence.
UV light damages DNA by causing
-covalent bonds to form between two -cytosines next to each other on the same DNA strand. -covalent bonds to form between thymine nucleotides next to each other on the same DNA strand. -covalent bonds to form between two thymine nucleotides on opposing DNA strands.
The following are examples of changes in cell behavior. Determine whether they could result in cancer (unregulated cell growth) or not. COULD CAUSE CANCER WOULD LIKELY NOT CAUSE CANCER
-loss of an essential checkpoint protein CANCER -los of the tumor-suppressor p53 CANCER -blocking of DNA polymerase NOT CANCER -increase in accuracy of DNA replication NOT CANCER -activation of p53 NOT CANCER -slight increase in apoptosis NOT CANCER .
The following are examples of the activities of some DNA repair mechanisms. Sort the examples into the appropriate category. (Note: 8-oxoG is a damaged G base.) DIRECT REPAIR NUCLEOTIDE EXCISION REPAIR METHYL-DIRECTED MISMATCH REPAIR
-removal of 8-oxoG NOT DIRECT -removal of an alkyl group from a G NOT METHYL -recognition of a TT dimer NOT DIRECT -removal of a damaged A base NOT METHYL -recognition of a mismatched G-T base pair shortly after replication NOT NUCLEOTIDE
Sequence the following steps in the development of cancer in an individuals with xeroderma pigmentosum (XP). metastasis mutation of a tumor-suppressor gene exposure to UV light mutation in DNA repair enzyme gene benign growth malignant growth
1.MUTATION IN DNA REPAIR ENZYME GENE 2.EXPOSURE TO UV LIGHT 3.MUTATION OF A TUMOR SUPPRESSOR GENE 4. BENIGN GROWTH 5.MALIGNANT GROWTH 6.METASTASIS
Which of the following mutations might result in the formation of an oncogene?
A cell has a damaged segment of DNA, however p53 proteins are mutated so that they cannot bind to the DNA and activate transcription factors that would stop the cell cycle.
Which of the following could not result from a mutation?
A fish in a stream dies from a poison that blocks cellular respiration
Which of the following mutagens might increase the incidence of slipped-strand mispairing?
A mutagen that caused a tautomeric shift A mutagen that caused thymine-dimers A mutagen that stabilized single-stranded DNA A mutagen that disabled DNA repair enzymes
What mutation would allow the cell to divide when it should not and could possibly lead to cancer?
A mutation causing p53 to activate p21, even when it is not necessary. None of these will lead to cell proliferation. A mutation preventing p21 from dissociating from cyclin. A mutation causing p21 to remain active, even in the absence of a signal from p53.
Which mutation would allow the cell to pass the G1 checkpoint when it should not?
A mutation in Rb, preventing it from associating with E2F. A mutation in RB, preventing it from becoming phosphorylated. A mutation in CDK, preventing in from phosphorylating Rb. A mutation in Rb, preventing it from dissociating with E2F.
Mutations in the protein retinoblastoma (Rb) are often associated with cancer in the eye. What mutation might lead to cancer?
A mutation that prevents Rb from interacting with myc. A mutation that prevents Rb from interacting with a kinase. A mutation that prevents Rb from dissociating from the protein myc. All of these mutations will cause cancer.
What result is characteristic of slipped-strand mispairing mutation?
A protein that, starting at the point of the deletion, has incorrect amino acids and is of abnormal length. A protein of normal length that has many altered amino acids in the center of the protein. A protein that is abnormally long with random amino acids added at the N-terminus. A protein that is missing amino acids at its N-terminus.
A young girl was born with a patch of soft fur that ran from the base of her neck to her tailbone. She did not display any other symptoms of disease, and results of her karyotype seemed normal. No one on either her mother or father's side of the family had ever been born with this oddity. Her concerned mother's side asked a doctor if her daughter would have children that were similarly furry. The doctor told her that while he couldn't be 100% certain, he suspected that this characteristic was the result of
A somatic mutation that occurred in the developing embryo, but probably wouldn't affect the daughter's egg cells
Mutations in the gene that codes for the protein p53 have been implicated in many types of cancer. The p53 protein has a diverse regulatory role, including stopping the cell type at G1/S checkpoint when there is damaged DNA, inducing NER mechanisms, and initiating apoptosis. Which of the following mechanisms might result in reduced levels of functional p53 in the cell?
A virus, such as HPV, inactivates p53 Mutation in the promoter region of the p53 gene, causing an enhancer to be permanently bound to the DNA Gene amplification that leads to an abnormally large number p53 genes in the genome All of these will lead to reduced levels of the p53 protein in the cell.
Which of the following statements about repair of thymine dimers is TRUE?
All of these are TRUE Light repair is an exergonic process and does not require any energy input. Excision repair can be used to repair thymine dimers as well as other types of damaged DNA. Excision repair is an exergonic process and required energy input in the form of light.
Which of the following is an example of a mutation?
An A-T base pair in a gene is changed to a G-C base pair
Why is breast cancer a very deadly form of cancer?
Because some people are born with mutations in the BRCA tumor suppressor genes. Because the breast is a vital organ that humans cannot survive without. Because breasts contain numerous blood vessels and lymph nodes, so breast cancer can easily metastasize and spread throughout the body. Because the breasts are very close to the heart and lungs, which are vital organs that humans cannot survive without.
Why are people afflicted with zeroderma pigmentosa?
Because they are born with a mutation in their DNA repair system and one of their proto-oncogenes has been mutated into an oncogene. Because they are born with a mutation in their DNA repair system. Because they are born with a mutation in their DNA repair system and they cannot repair DNA that is mutated by UV radiation. Because one of their proto-oncogenes has been mutated into an oncogene.
What characteristic of DNA makes nucleotide excision repair (NER) mechanisms possible?
DNA is wrapped around histone proteins that can influence its accessibility to proteins. DNA is a double helix so once a damaged region is recognized, it can be removed and synthesized based on the undamaged opposite strand. DNA may have enzymatic activity. DNA is an information storage molecule.
What enzyme is responsible for repairing thymine dimers using the energy of light?
DNA ligase DNA exonuclease DNA photolyase DNA Polymerase, DNA ligase, and DNA exonuclease
Which of the following is not a mechanism by which viruses could cause cancer?
DNA of the virus could insert into the coding region of a tumor-suppressor gene, inactivating it. A protein made by the virus could activate a cell division pathway. Infection by a virus could cause the immune system to kill the infected cells by apoptosis. A virus could insert DNA in a promoter of a proto-oncogene, causing the resulting oncogene to become overexpressed.
Which of the following is not a reason why cells need to be able to repair damaged DNA?
DNA polymerase may not be able to replicate DNA if there is damage The function of an essential gene could be lost if the DNA is not repaired Without repair systems, the rate of mutations would be too high Cells need to change base pairs to be able to express different types of proteins
You want to test the mutagenicity of a certain chemical that you suspect causes changes to DNA molecules. You have not been able to locate the Salmonella typhimurium strain that requires histidine in order to grow. What might you be able to use instead?
E. coli bacteria that contain a point mutation in a gene that encodes an enzyme required in the arginine biosynthetic pathway. E. coli bacteria that contain a gene amplification mutation of an enzyme involved in the arginine biosynthetic pathway. E. coli bacteria that contain a deletion of a gene that encodes an enzyme required in the arginine biosynthetic pathway. E. coli bacteria that contain a plasmid that confers antibiotic resistance.
Which of the following statements regarding the repair of thymine dimers is TRUE?
Excision repair of thymine dimers is possible because there are two strands of DNA. Repair of thymine dimers prevents DNA replication or transcription from occurring. Repair of thymine dimers requires the presence of light as an energy source for repair.
Cancer progression can result from mechanisms other than mutation (change in the DNA sequence). Which of the following is not an example of such a mechanism?
Exposure to chemicals that block activity of a tumor-suppressor protein. Chromosomes could become lost from cells during mitosis. Methylation of promoter DNA could block expression of a tumor-suppressor gene. Chromosomes could be lost during meiosis.
A cell that is in an environmentally that has an abnormally low pH will NOT pass which checkpoint?
G1
The cell cycle is regulated by checkpoints during the _______ phases.
G1, S and M G1, S and G2 G1, G2, and M G1, S, G2 and M
When a tautomeric shift occurs, which of the following is TRUE?
In the new DNA strand, purine is always replaced by a pyrimidine, and a pyrimidine is always replaced by a purine. The resulting mutation is always corrected by the proofreading ability of DNA polymerase. The result is always a frame shift mutation, leading to production of an abnormally short protein. In the new DNA strand, a purine is always replaced by a purine, and a pyrimidine is always replaced by a pyrimidine. Reference links
How does myc become active?
It is phosphorylated. It is dephosphorylated. It is activated by Rb. It is activated by a cyclin dependent kinase.
DNA repair enzymes will be highly active during what phase of the cell cycle?
Mitosis G1 G2 Cytokinesis
Which of the following statements about oncogenes is FALSE?
Multiple Choice Oncogenes may be the result of a viral infection. When oncogenes are silenced, the cell cycle may be able to proceed even when it should not. Oncogenes may occur due to a mutation in a gene regulatory region, such as a promoter, enhancer, or repressor. Oncogenes are mutated versions of a gene that occurs in a healthy individual.
Below are the results of the Ames test for mutagenicity for three different mutagens, X, Y, and Z. Which of the following statements is FALSE? .
Mutagen Z may not be mutagenic. Mutagen Y is the least mutagenic. The test for mutagen X is probably compromised because there is only 1 colony on the positive control. .
You are examining a gene that normally has the sequence ACGATTTGGCGC But in the mutant fruit fly you have produced, you see the sequence ATGATTTGGTGT What likely caused this mutation?
Mutations induced by HNO2
CCR5 is a cell surface receptor protein of white blood cells that attracts them to specific tissue and organs to elicit an immune response. It is also the receptor to which R5 strains of HIV bind to and enter T cells. Between 5-14% of people from Northern European descent possess an allele known as CCR5-Δ32. In this allele, a 32 base pair section of the gene has been deleted. What phenotype would you predict for people carrying the CCR5-Δ32 allele?
People with CCR5-Δ32 will likely have impaired immune function, but will have resistance to HIV infection. People with CCR5-Δ32 will likely have strong immune function, and will have resistance to HIV infection. People with CCR5-Δ32 will likely die before birth. People with CCR5-Δ32 will likely have impaired immune function, and will be very susceptible to HIV infection.
Which of the following statements about the repair mechanism involving photlyase is TRUE?
Photolyase is reduced and the damaged DNA is oxidized. Photolyase phosphorylates the damaged DNA. Photolyase is oxidized and the damaged DNA is reduced. Photolyase dephosphorylates the damaged DNA.
Cancer cells often are missing chromosomes. How could loss of chromosomes result in cancer?
Proto-oncogenes are lost from the missing chromosomes. The remaining chromosomes express tumor suppressor genes. The missing chromosomes could have contained tumor-suppressor genes. A missing chromosome could cause the cell cycle to stop.
In the Ames test for mutagenicity, why was rat liver extract included in the control sample?
Rat liver extract serves as an indicator for mutagenicity. It allows scientists to count the mutated colonies in each sample. Rat liver extract was being tested for its mutagenic properties Rat liver extract contains enzymes that may be necessary for certain mutagens to work. Since it must be added to the experimental sample, it is also added to the control sample. Bacterial cells can only make the amino acid histidine if rat liver extract is present
The gene that codes for a certain caspase enzyme has a point mutation so that it can no longer degrade certain proteins. This will result in
Silencing of a tumor suppressor gene Conversion of a proto-oncogene to an oncogene Formation of an oncogene due to a viral infection
A carcinogen is a chemical or treatment that
causes mutations that can affect gene activity.
A nucleotide deletion in DNA replication
causes one amino acid of the protein to be incorrect. causes all of the amino acids of the protein to be incorrect. causes the amino acids inserted before the deletion to be incorrect. has no effect on the resulting protein.
Growth factor receptors are typically found in the
cell membrane cytoplasm nucleus Golgi apparatus
A mutation that causes a change in a single nucleotide in DNA
changes the corresponding nucleotide in mRNA, resulting in a different codon.
