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Adjacent deoxyribonucleotides on one strand of a double-stranded DNA molecule are connected by which of the following types of chemical bonds?

Phosphodiester Bonds


p16 is a member of the INK family of CDK inhibitor proteins (CIP). It functions by binding to CDK4 and CDK6. What effect does the action of p16 have on the cell cycle?

A. p16 promotes the associations between CDK4/6 and cyclin D.
B. p16 triggers the release of E2F from RB.
C. p16 blocks passage of cell cycle through restriction point in late G1.
D. p16 promotes the hyperphosphorylation of RB.

C − Binding of p16 to CDK4 and CDK6 prevents them from associating with cyclin D. Without active cyclin D-CDK4/6 complexes, cells cannot pass the restriction point in late G1.


A mutation resulting in a nucleotide substitution was observed within the open reading frame of a gene. When the protein produced from this gene was analyzed, it was found that no changes in amino acid sequence were present. Which of the following characteristics of the genetic code accounts for these observations?

A The genetic code is nonoverlapping.
B The genetic code is not punctuated.
C The genetic code is degenerate.
D The genetic code is a triplet code.
E The genetic code is essentially universal among species.

C − The degenerate nature of the genetic code means that some amino acids are represented by multiple codons. For example, phenylalanine is coded for by TTT and TTC. If a mutation alters the third T in the codon to C, then no amino acid change would be observed. This is known as a silent mutation.


A strain of bacteria resistant to a specific antibiotic was isolated in a hospital laboratory. Biochemical analysis demonstrated that treatment of the sensitive strain with the antibiotic resulted in a block in bacterial RNA synthesis, whereas in the resistant strain, RNA synthesis was unaffected. The resistant strain is unaffected by which of the following drugs?

A Chloramphenicol
B Tetracycline
C Rifampicin
D Acyclovir
E Amoxicillin

C − Rifampicin inhibits initiation of RNA synthesis by RNA polymerase holoenzyme in bacteria.

A Chloramphenicol is a broad-spectrum antibiotic that inhibits protein synthesis at the elongation phase by inhibiting peptidyl transferase activity of the bacterial ribosome.

B Tetracyclines bind to the small 30S subunit of bacterial ribosomes and inhibit translational elongation.

D Acyclovir is an inhibitor of viral DNA replication; it is not active against bacteria.

E Amoxicillin is a beta-lactum antibiotic that inhibits bacterial cell wall synthesis by blocking the cross-linking of peptidoglycan polymers.


A recent report identified a G --> C transversion in the gene encoding the hematopoietic transcription factor GATA1 in the genome of a patient with the congenital syndrome Diamond-Blackfan anemia. The deletion caused a loss of exon 2 in the transcribed mRNA. Biochemical analysis of cells homozygous for this mutation indicated that no functional GATA1 protein was produced. What is the likely location of the nucleotide substitution in the GATA1 genes of this patient?

A 5'-UTR
B 3'-UTR
C Splice donor site
D Promoter
E Enhancer

C − Mutations in intron-exon boundaries that affect splicing tend to cause loss of exons in the transcribed mRNA. In this case, the loss of exon 2 leads to the production of GATA1 that lacks the transactivation domain.


A novel drug that binds the 30S subunit of prokaryotic ribosomes was found to have bactericidal activity in laboratory tests and is proposed for clinical trials. Studies were performed in which bacterial cultures were treated with high doses of this drug, followed by biochemical analysis. Drug treatment was found to cause a significant reduction in the initiation phase of protein synthesis. The tested drug has a mechanism of action similar to which of the following antibiotics?

A Cycloheximide
B Puromycin
C Chloramphenicol
D Dihydrostreptomycin
E Tetracycline

D − Streptomycin inhibits protein synthesis by binding to the 16S rRNA of the 30S subunit to disrupt the assembly of the 70S ribosome, mRNA and aminoacyl-tRNA to form the initiation complex.


During protein synthesis, the energy for peptide bond formation comes from which of the following chemical bonds?

A The ester bond joining the amino acid and the terminal ribose of tRNA, broken during peptide synthesis

B The phosphodiester bond of adenosine triphosphate (ATP), hydrolyzed by the catalytic rRNA.

C The phosphodiester bond of guanosine triphosphate (GTP), hydrolyzed by an elongation factor

D The phosphodiester bond of GTP, hydrolyzed by an initiation factor

E The phosphodiester bond of GTP, hydrolyzed by a release factor

A − During the charging of tRNAs by aminoacyl tRNA synthetases, ATP is consumed to form an ester bond between the 3'-OH of the terminal adenosine of tRNA. The energy stored in this bond is then consumed to form a peptide bond during protein synthesis.


Which type of mutation in a codon would lead to recruitment of release factor to the ribosome when the codon is present in the A site?

D − Nonsense mutations are those that result in the generation of a stop codon in place of an amino acid codon. When a stop codon is present in the A site of a ribosome, it leads to recruitment of release factor, which triggers peptidyl transferase to cleave the ester bond between the peptide's C terminus and the tRNA in the P site.


The overexpression of BCL-2 observed in certain types of B cell lymphoma serves as one of the first and strongest forms of evidence that failure of cell death contributes to cancer. Tumors expressing high levels of BCL-2 (and other antiapoptotic family members) are frequently found to be resistant to radiation therapy and chemotherapeutic agents. Early advances in BCL-2 targeted therapy involved the use of antisense technology that aimed at inhibiting BCL-2 expression. One promising antisense oligonucleotide was G3139 (oblimersen). Which experimental result would provide evidence that G3139 is effective at overcoming the antiapoptotic effects of elevated BCL-2 in B cell lymphoma?

A. Organization of the cytoskeleton remains unchanged
B. A decrease in the cleaved form of caspase-3
C. An increase in the cleaved form of caspase-9
D. An increase in BCL-2 mRNA
E. An increase in the number of cells that swell and burst

C − Overexpression of BCL-2 would prevent the cleavage of caspase-9 into its active form. Thus, G3139 may be deemed effective if its use results in an increase in the cleaved form of caspase-9.


A 31-year-old man who emigrated from Vietnam and recently returned from a visit to his home country presents in your office with a chief complaint of sore throat, fever, and malaise. Upon physical examination, you observe a gray membrane that covers his tonsils and pharynx. Upon questioning, you find that he has never been vaccinated for diphtheria. In cells exposed to the toxin, which of the following processes related to gene expression are affected as a direct result of the action of the diphtheria toxin?

A Transcriptional initiation
B Transcriptional elongation
C Transcriptional termination
D Translational initiation
E Translational elongation

E − Diphtheria toxin catalyzes the covalent attachment of ADP to the catalytic unit of eEF-G, irreversibly inactivating it. Translocation, and therefore elongation, is blocked in eukaryotic cells.


A mutation in a gene coding for a specific type of RNA molecule from which class of eukaryotic RNAs could potentially cause amino acid misincorporations in a wide variety of proteins?

A 18S ribosomal RNA (rRNA)
C Micro RNA (miRNA)

E − tRNA "charging" is governed by "acceptor identity," which constitutes in essence a second genetic code. Specifically, the tRNA synthetase enzymes recognize both the amino acid and its cognate tRNA by sensing a particular three-dimensional conformation. As such, a mutation in a tRNA could potentially alter its structure such that the mutant tRNA is recognized by an incorrect tRNA synthetase that "charges" the mutant tRNA with the wrong amino acid.


A physician is exploring the best treatment options for his 56-year-old female patient who has been diagnosed with breast cancer. To show that his patient may be a good candidate for Herceptin, he plans to examine a biopsy of her cancerous tissue for expression levels of which of the following proteins?

A BCR-ABL tyrosine kinase
B HER2/NEU family of receptors
C Insulin receptors
D FAS receptors

B − Herceptin (trastuzumab) is a monoclonal antibody directed against HER2/NEU receptors (which are members of the EGF family of receptors).


Six weeks after possible exposure to the human immunodeficiency virus (HIV), a 28-year-old man visits his doctor to request an HIV test. Blood was drawn, and an enzyme-linked immunosorbent assay (ELISA) for specific HIV antigens was positive. What additional antigen-antibody test must be performed to rule out the possibility that the ELISA result was false-positive?

A Southern blot
B Western blot
C DNA microarray
D Fluorescence in situ hybridization (FISH)
E Northern blot

B − The Western blot (immunoblot) is the gold standard for validation of HIV infection and is used to confirm the results of an ELISA. It allows for the detection of some circulating HIV proteins whose levels increase prior to the appearance of anti-HIV antibodies (which are detected in HIV ELISAs).


During the elongation phase of prokaryotic translation, for each amino acid added to the growing peptide chain, two GTP molecules are hydrolyzed to GDP. Which of the following aspects of ribosome function require the hydrolysis of one of these GTP molecules?

A Peptide bond formation
B Aminoacyl-tRNA delivery to A site
C Binding of CAP-binding complex to the 7-methyl-guanosine cap of mRNA
D Assembly of the small and large ribosomal subunits

B − One GTP molecule is hydrolyzed by the G protein elongation factor-1 (EF-1 in eukaryotes) when an amino acyl tRNA is inserted into the A site. A second is expended during the translocation process.


A 65-year-old woman presents to her physician complaining of fatigue, lack of energy, and weight loss. Physical exam reveals splenomegaly, and laboratory tests indicate an elevation in white blood cell count. Bone marrow analysis reveals the presence of a shortened version of chromosome 22 caused by a reciprocal translocation of DNA between chromosomes 9 and 22.Which of the listed drugs is a suitable first-line therapeutic agent to treat this patient's condition?

A Trastuzumab (Herceptin)
B Imatinib (Gleevec)
C Cetuximab (Erbitux)
D Infliximab (Remicade)
E Basiliximab (Simulect)

B − The patient has chronic myelogenous leukemia (CML), which is driven by the unregulated tyrosine kinase activity of the BCR-ABL protein product of the Philadelphia chromosome (der 22). Imatinib binds to the active site of the ABL tyrosine kinase and inhibits its activity.


A 7-methylguanosine residue is found on the 5' end of the product of which of the following enzymes?

A RNA polymerase I
B RNA polymerase II
C RNA polymerase III
D DNA polymerase alpha
E DNA polymerase delta

B − A 7-methylguanosine cap is added to the 5' end of mRNAs following their synthesis. RNA polymerase II synthesizes mRNA in eukaryotic cells.


While working in a medical mission in a small village in Honduras, a 7-year-old male child is brought to you by his parents. The parents tell you that the child has always had "very bad skin and been very sick," and whenever they can afford it, they take the boy to a hospital in the nearest city for treatment of his skin lesions. While the child was still an infant, the doctors told the parents that he cannot ever be exposed to sunlight, a restriction that is difficult to impose as both parents work in the fields all day. Upon examination of the boy, you find significant patches of discolored skin with areas of severe blistering on his face, arms, and neck that are oozing and raw (indicative of xeroderma pigmentosum). Molecular analysis of the DNA from the boy's skin keratinocytes would reveal an abundance of which of the following types of lesions?

A Double-stranded breaks
B Pyrimidine dimers
C Chromosomal translocations
D Nucleotide deletions
E Nucleotide substitutions

B − The boy has the genetic condition xeroderma pigmentosum due to a defect in nucleotide excision repair. The most common form of DNA damage resulting from sunlight exposure is the production of thymidine dimers. Nucleotide excision repair recognizes and removes bulky adducts that alter or distort the normal shape of DNA, which includes thymidine dimers.


What effect does damage to DNA have on p53 protein?

A Inactivates p53
B Stabilizes p53
C Degrades p53
D Dephosphorylates p53

B − DNA damage triggers the phosphorylation and thus stabilization of p53.


Which of the following mutations is an example of a "gain of function" mutation that converts a normal gene (proto-oncogene) into an oncogene that leads to the production of oncoproteins?

A A mutation in BRCA1/BRCA2 that disrupt homologous recombination

B A mutation in p53 that prevents its phosphorylation in response to DNA damage

C A mutation in NF-1 that prevents activated RAS protein from being turned off

D A point mutation in HER2 that allows the protein product to signal in absence of ligand

E A microdeletion in RB that results in loss of control of the G1 checkpoint

D − HER2 is a proto-oncogene that encodes HER2 (a member of the family of epidermal growth factor receptors). A point mutation in HER2 that changes a valine to glutamine converts it into an oncogene whose oncoprotein product is Neu. The dimerization of tyrosine kinase activity of Neu is triggered in the absence of ligand.


Valproic acid is a drug used clinically to treat seizures. Biochemically, it is an inhibitor of histone deacetylases. Treating cells with valproic acid will likely alter the charge of which of the following amino acids in histones?

A Aspartate
B Glutamate
C Histidine
D Arginine
E Lysine

E − Histones are rich in the basic amino acids arginine and lysine. Acetylation occurs only on the positively charged amino groups of lysine residues. This neutralizes the basic charge and reduces the affinity of DNA for nucleosomes, making it more accessible to the transcriptional machinery.


Which of the following events is characteristic of both the extrinsic and intrinsic pathways of apoptosis?

A Activation of caspase 8

B Cleavage of the proapoptotic factor, BID

C Involvement of Fas-associated death domain protein (FADD)

D Activation of caspases 3, 6, and 7

D − Caspases 3, 6, and 7 are activated by both the extrinsic and intrinsic pathways of apoptosis.


The public health department in your state recently reported the isolation of a tetracycline-resistant strain of Treponema pallidum in your area. Biochemical analysis has determined that the resistance is associated with a change in ribosome structure, which alters the ribosome'™s function. Which of the following functions in protein synthesis is most likely to be altered in the tetracycline-resistant strain of T. pallidum?

A Assembly of the 30S preinitiation complex

B Entry of the 50S ribosomal subunit to create the initiation complex

C Binding of aminoacyl-tRNAs to the A site

D Peptidyl transferase activity of the 70S ribosome

E Translocation of the 70S ribosome

C − Tetracylclines bind to the small 30S subunit of bacteria, blocking access of aminoacyl-tRNAs to the A site. An alteration in ribosome structure, perhaps affecting the A site, could potentially disrupt the binding of tetracycline to the ribosome, generating a resistant phenotype.


A colleague claims that inhibition of DNA primase would block initiation of new DNA synthesis at origins of replication but would not affect ongoing DNA synthesis. For which of the following reasons is your colleague incorrect?

A DNA synthesis is bidirectional.
B DNA synthesis is semidiscontinuous.
C DNA synthesis requires a primer for DNA polymerase I to extend.
D DNA synthesis requires strand separation by helicase.
E DNA synthesis is semiconservative.

B − DNA polymerase can synthesize DNA only in a 5'-->3' direction. On one strand of the DNA molecule (the lagging strand), the polymerase synthesizes a series of short DNA polymers (Okazaki fragments) that each require a primer. Therefore, new primers synthesized by primase are required for ongoing DNA synthesis, not just when DNA synthesis initiates at origins of replication.


Meningitis is a rare and very serious complication of tularemia, which is caused by Francisella tularensis infection. Antibiotic drugs inhibit protein translation in prokaryotes by interfering with the initiation, elongation, or termination phase. One treatment modality for the treatment of tularemia is the antibiotic chloramphenicol in combination with one other antibiotic that inhibits a different phase of protein translation. Which of the following drugs would be the appropriate choice to pair with chloramphenicol?

A Erythromycin
B Puromycin
C Tetracycline
D Streptomycin
E Cycloheximide

D − Streptomycin inhibits protein synthesis at the initiation phase by binding to the small ribosomal subunit and inhibiting assembly of the preinitiation complex. Because chloramphenicol inhibits the elongation phase (by blocking peptidyl transferase activity), the two drugs inhibit different aspects of translation and are synergistic.


A nucleotide sequence 5'-TCCGAT-3' within human genomic DNA underwent spontaneous mutation resulting in a nucleotide substitution, producing the sequence 5'-TTCGAT-3'. Which one of the following chemical reactions could account for the nucleotide substitution above?

A Conversion of a deoxyribosyl group to a ribosyl group

B Deamination of a pyrimidine

C Hydrolysis of the N-glycosidic bond in a purine

D Hydrolysis of a phosphodiester bond

E Methylation of a cytosine

B − Deamination of cytosine converts the base to a uracil. Uracil will be replaced by thymidine either by repair mechanisms or during the next round of DNA replication.


The DNA translocation generating the Philadelphia chromosome involves which proto-oncogene and is diagnostic for which disease?

A RAS G protein, colon carcinoma

B RAS G protein, chronic myelogenous leukemia

C c-MYC transcription factor, Burkitt'™s lymphoma

D ABL tyrosine kinase, chronic myelogenous leukemia

E p53 transcription factor, chronic myelogenous leukemia

D − The Philadelphia chromosome (der (22)) results from the reciprocal translocation of the abl proto-oncogene from chromosome 9 to chromosome 22 and the BCR region of chromosome 22 to 9. This translocation creates a BCR-ABL fusion gene (and an unregulated tyrosine kinase protein product) and is associated with chronic myelogenous leukemia (CML).


Cyclin D—dependent kinases (CDK4/6) are key targets for cancer chemotherapy. The compound palbociclib, or PD 0332991, is a selectively potent inhibitor of CDK4 and CDK6 in retinoblastoma protein (RB)—positive cancer cell lines. Studies show that oral administration of PD 0332991 to mice harboring human tumor xenografts resulted in a broad spectrum of anticancer activity and caused the regression of certain tumors. Which of the following effects would be a consequence of treatment with PD 0332991?

A Progression of tumor cell cycle through the G1-S phase

B Stimulation of RB phosphorylation

C Reduction in the transcription of genes under the control of E2F

D Arrests cells in the G2 phase

E Promotion of E2F release

C − Inhibition of CDK4/6 by PD 0332991 inhibits the phosphorylation of RB in tumor cells. Consequently, E2F remains sequestered by RB and unable to promote the transcription of target genes.


Which one of the following antibiotics will inhibit cytoplasmic protein synthesis in both prokaryotic and eukaryotic organisms?

A Erythromycin
B Tetracycline
C Streptomycin
D Chloramphenicol
E Puromycin

E − Puromycin acts upon both eukaryotic and prokaryotic peptidyl transferases, releasing small peptides ending in puromycin at their C-terminal ends.


Following a day spent at the beach, which of the following types of DNA damage would most commonly be found in melanocytes within the basal layer of the epidermis?

A Apurinic sites caused by depurination
B Intrastrand cross-links
C Double-strand breaks
D Pyrimidine dimers
E Nucleotide alkylation

D − Ultraviolet (UV) radiation in sunlight most commonly causes the formation of pyrimidine dimers.


Fabry disease is an X-linked recessive disorder caused by defects in the activity of the lysosomal enzyme alpha-galactosidase. This results in the accumulation of glycolipids in the plasma and cellular liposomes of the brain, heart, and kidneys. Patients affected by Fabry disease present with raphes, peripheral neuropathy, cardiac disease, and kidney failure. The pedigree below shows inheritance of the X-linked recessive Fabry disease. Which statement is a correct interpretation of this family's pedigree?

A Both males and females of all generations are affected.

B All female descendants of the affected male are carriers.

C Sons of heterozygous mothers have a 50% chance of being affected.

D The genetic mutation cannot be passed on to great-grandchildren (third generation).

C − For X-linked disorders, sons of heterozygous mothers (i.e., carriers) have a 50% chance of having the disorder.


How do genetic mutations in proto-oncogenes contribute to cancer?

A They alter the structure or amount of the gene's protein product.

B They disrupt the protein product'™s ability to repair damaged DNA.

C They disrupt the protein product'™s ability to arrest the cell cycle.

D They cause a reduction in the amount of the gene'™s protein product.

A − Mutations in proto-oncogenes that change their structure or increase their level of expression contribute to the development of cancer.


Which of the following DNA sequences (only one strand of the double-stranded sequence is shown) would have the greatest thermal stability?


E − This sequence has the greatest number of G:C base pairs (seven total). G:C base pairs are held together by three hydrogen bonds, compared with two hydrogen bonds for A:T base pairs, and therefore require more energy (heat) to denature.


A 34-year-old woman whose mother died from breast cancer and whose sister was recently diagnosed with the disease comes to you for genetic testing. The results of the tests indicate she has a homozygous mutation in her BRCA1 genes. To which types of DNA damaging agents will this woman be particularly sensitive?

A Alkylating agents
B Intercalating agents
C Medical X-rays
D Sunlight
E Adduct forming agents (e.g., benzo(a)pyrene)

C − BRCA1 codes for a protein involved in the homologous recombination repair pathway. This pathway is particularly important in repairing double-stranded breaks in the DNA. Ionizing radiation, such as X-rays, are capable of producing double-stranded breaks (among other types of damage).


The antineoplastic drug 5-fluorouracil (5-FU) can be metabolized in cells to 5-fluorouridine triphosphate (5-FUTP), whose structure is shown below. Which of the following enzymes would use 5-FUTP as a substrate?

A DNA polymerase
B Protein kinase
C Ribosome (peptidyl transferase activity)
D RNA polymerase
E Telomerase

D − 5-FUTP is a ribonucleoside triphosphate and therefore can be incorporated into RNA by RNA polymerases.


Lentiviral particles such as the human immunodeficiency virus (HIV) contain an RNA genome. Upon infection, the RNA is converted into double-stranded DNA, which integrates into the host cell's genome. Which enzyme is responsible for the conversion of the RNA genome into DNA?

C − Reverse transcriptase is an RNA-dependent DNA polymerase that copies the retrovirus's™ RNA genome into complementary DNA (cDNA). This enzyme action is inhibited by the chain terminator, azidothymidine (AZT).


When the ribosome reaches a stop codon on mRNA, release factors act to change the specificity of peptidyl transferase so that the growing peptide chain is transferred to which of the following moieties?

A Water
C Formyl-methionine
E The E site

A − Release factors interact with peptidyl transferase, allowing it to transfer the nascent polypeptide chain to water instead of to the alpha amino group of an incoming aminoacyl tRNA.


One mechanism of potential mutation is the insertion of an incorrect nucleotide by DNA polymerases delta and epsilon into the newly synthesized DNA molecule. Which of the following enzymes, present at the replication fork, repairs nucleotide misincorporation by DNA polymerase delta during DNA synthesis?

A DNA ligase
B DNA helicase
C DNA topoisomerase
D DNA polymerase delta
E DNA polymerase alpha

D − DNA polymerase delta has 3'--> 5' exonuclease (proofreading) activity that allows the enzyme to backtrack and remove a misincorporated nucleotide and insert the correct nucleotide.


A 2-year-old male patient was brought to the physician by his mother, who stated that her son's left eye had a glow similar to that of a cat's eye caught in headlights. She also noticed that his eyes appeared crossed, and he appears to have diminished vision in his left eye. The physician sends the child to an ophthalmologist, who confirms that the child has tumors in his retina. What is the most likely cause of this patient's condition?

A "loss of function" mutation in the p53 gene

B chromosomal translocation involving the BCR and ABL genes

C "gain of function" mutation in the RAS gene

D "loss of function" mutation in the RB gene

E point mutation in the N-MYC gene

D − This patient has retinoblastoma marked by tumors in the retina. Retinoblastoma is linked to "loss of function" mutations and deletions in the RB gene.


You must evaluate the genetic status of a family with a history of Huntington disease and wish to determine the number of triplet repeats in each individual. What would be the best way to estimate the number of triplet repeats?

A Real-time polymerase chain reaction (RT-PCR)

B cDNA library construction

C Variable number of tandem repeat (VNTR) analysis

D Restriction fragment length polymorphism (RFLP) analysis

C − Huntington disease is associated with the presence of a variable number of tandem repeats (VNTR) regions in which the sequence CAG is found repeated between 37 and 100 times.


A 29-year-old woman presents at the clinic with a chief complaint of joint pain of 8 weeks'™ duration. She also reports loss of appetite, fatigue, and general malaise of similar duration. More recently, she noted her hair was thinning in places, which spurred her to visit the doctor. Upon physical examination, you observe several red, scaly, disc-shaped lesions on her scalp and face, indicative of systemic lupus erythematosus (SLE). You order blood work and suspect the test may find autoantibodies directed against components of the cellular machinery responsible for which of the following processes?

A DNA synthesis
B RNA splicing
C Protein synthesis
D RNA synthesis
E DNA recombination

B − Antibodies against small nuclear ribonucleoproteins (snRNPs)—the components of the RNA spliceosome, which splices out introns from pre-mRNA molecules and ligates the exons together to form functional mRNAs—are frequently found in the serum of patients with SLE.


Sometimes the gene responsible for a particular genetic disease has not yet been cloned, so researchers must use a probe that is genetically linked to the gene they wish to follow. If a new restriction fragment length polymorphism (RFLP) is detected using a probe linked to the gene, this result may be interpreted to mean

A that a mutation has not occurred

B that the activity of the gene'™s protein product will not change

C that a mutation has occurred in the gene or in the region flanking the gene

D that the recognition sequences for restriction enzymes are unchanged

C − Detection of a new RFLP means that the length of the DNA fragment that hybridizes to the probe is different; therefore, a mutation has occurred. However, without additional information, it is not possible to determine the location of the mutation itself.


A 7-methylguanosine residue is found on the 5' end of the product of which of the following enzymes?

A RNA polymerase I
B RNA polymerase II
C RNA polymerase III
D DNA polymerase alpha
E DNA polymerase delta

B − A 7-methylguanosine cap is added to the 5$ \prime $ end of mRNAs following their synthesis. RNA polymerase II synthesizes mRNA in eukaryotic cells.


An investigator is comparing the properties of the eukaryotic 80S and prokaryotic 70S ribosomes. However, during the preparation of ribosomal samples, he neglects to label the tubes and is unsure which tube contains the prokaryotic ribosomes and which contains the eukaryotic ribosomes. He suspects the tube labeled A contains the 80S ribosomes. Which antibiotic would inhibit protein synthesis in tube A and thus unambiguously identify it as the tube containing 80S ribosomes?

A Chloramphenicol
B Cycloheximide
C Erythromycin
D Puromycin
E Tetracycline

B − Eukaryotic (80S) ribosomes are inhibited by cycloheximide, whereas prokaryotic (70S) ribosomes are not.


Which of the following observations is evidence for semiconservative DNA replication?

A DNA synthesis proceeds in the 5'-->3' direction.

B DNA synthesis occurs on both lagging and leading strands in the replication fork.

C After DNA synthesis, each daughter molecule contains one parental strand and one new strand.

D During DNA synthesis, replication proceeds in both directions from the origin of replication.

E DNA synthesis in eukaryotes requires the activity of more than one DNA polymerase enzyme.

C − During semiconservative replication, the parental DNA molecule is unwound (by the helicase enzyme), and the two single strands serve as templates for synthesis of new DNA. After synthesis is complete, the resulting two DNA molecules contain one parental strand and one newly synthesized strand; that is, the parental strand is "semiconserved" in the daughter strand.


Li-Fraumeni syndrome (LFS) is an autosomal dominant inherited cancer syndrome characterized by mutations in the p53 gene that prevents activation of the p53 protein product in response to DNA damage. Consequently, patients with LFS develop tumors early (before age 45), develop multiple types of tumors (in an individual), and have several relatives who have been diagnosed with any type of cancer before the age of 45. What is the possible consequence of a defective p53 in response to DNA damage?

A Sequestration of E2F by RB

B Decreased transcription of p21

C RB will be in a hypophosphorylated state

D Decreased transcription of cyclin A

E Cell cycle arrest

B − The transcription of p21 will be decreased when p53 is defective. When p53 retains its ability to become activated in response to DNA damage, it triggers the transcription of p21, which binds to and inactivates cyclin-CDK complexes (e.g., cyclin D-CDK2, cyclin E-CDK2). Inactivation of these complexes prevents the phosphorylation and inactivation of RB, thus allowing the hyperphosphorylated RB to sequester E2F. Sequestration of E2F prevents it from promoting the transcription of cyclins (cyclin A and cyclin E) that allow the cell cycle to transition through its various phases.
(p53 --> p21 - Cyclin D/E-CDK2 --> RB (hyperphosphorylated) --> E2F (release) --> Cyclin A/E transcription --> Cell cycle transition)


Following the treatment of cells with a low dose of the mushroom toxin alpha-amanitin, polyadenylated RNA in these cells was found to be decreased, whereas ribosome number and transfer RNAs (tRNAs) were unchanged. The activity of which of the following proteins is inhibited by low-dose alpha-amanitin?

A Transcription factor II D (TFIID)
B RNA polymerase II
C RNA polymerase III
D Histone acetyl transferase (HAT)
E Capping enzyme

B − RNA polymerase II, which synthesizes precursor messenger RNA (mRNA), is inhibited by low-dose \alpha-amanitin.


The following DNA sequence is the template for synthesis of newly transcribed RNA:

Which of the following sequences represents the RNA synthesized from the template?


A − RNA synthesis proceeds in the 5' -->3' direction. Therefore, the template strand is "read" by the RNA polymerase enzyme in the 3'-->5' direction, with the resulting RNA complementary to the DNA template.


Cells from a patient that cannot produce the enzyme GlcNAc phosphotransferase (which phosphorylates mannose on asparagine-linked oligosaccharide chains) would be unable to transport newly synthesized glycoproteins to which of the following locations?

A Extracellular space
B Lysosomes
C Plasma membrane
D Mitochondria
E Nucleus

B − Proteins destined for lysosomes are processed by the endoplasmic reticulum (ER) and Golgi such that they contain one or more phosphorylated mannose residues.


You are supervising a research team responsible for assessing novel anticancer drugs for the treatment of Wilms tumor (nephroblastoma) using cell culture lines taken from patients with the disease. Actinomycin D, currently used in the clinic for treating Wilms tumor, is your positive control treatment for assessing the efficacy of the novel compounds. RNA polymerase I is inhibited by doses of actinomycin D that are 50 to 100-fold lower than those needed to inhibit RNA polymerase II or III. One novel drug has the same efficacy as low doses of actinomycin D. In addition, you suspect the novel drug has a similar mechanism of action as actinomycin D because treating cells with either drug leads to dissolution of the nucleoli of the cells. If you are correct, which of the following RNA species in the cell will be diminished following treatment of the cells with low doses of the novel drug?


C − Actinomycin D intercalates between successive G:C base pairs of the DNA double helix and prevents movement of RNA polymerase I and thus inhibits the elongation phase of transcription. Treatment of cells with actinomycin D results in the dissolution of nucleoli, the site of rRNA synthesis. If the novel drug's mechanism is the same as actinomycin D, then it would also inhibit RNA polymerase I, and the levels of rRNA would diminish


Which of the following characteristics of nucleosomes is important for their ability to package genomic DNA into chromatin?

A The histone constituents of nucleosomes contain a relatively high proportion of lysine and arginine amino acids.

B Multiple posttranslational modifications can be present on multiple amino acids in the N-terminal regions of histones within nucleosomes.

C Nucleosomes consist of two copies each of histone H2A, H2B, H3, and H4

D The wrapping of DNA around nucleosome particles induces negative supercoils in the DNA molecule.

A − The relatively high percentage of positively charged lysine and arginine residues in histones facilitates wrapping of the negatively charged DNA molecule around the surface of the nucleosome.


A 26-year-old woman in generally good health comes to your clinic for a check-up, as she and her husband have decided to start a family. She is currently using a skin patch for transdermal delivery of low-dose synthetic estrogen and progesterone and will discontinue its use immediately. Both of these drugs activate gene transcription through mechanisms similar to another steroid family, glucocorticoids. At genes that are activated by estrogen, what changes in histone modification will likely occur in the short term (hours to days) once the woman discontinues her use of the contraceptive patch?

A Decreased acetylation
B Increased acetylation
C No change in acetylation
D Variable changes in acetylation, depending on the gene

A − The estrogen receptor functions in a manner similar to the glucocorticoid receptor. It is a ligand-activated nuclear transcription factor that binds DNA. The estrogen receptor recruits coactivators with histone acetyltransferase (HAT) activity to the genes it activates. The HAT enzymes acetylate histones on chromatin, leading to a decompacted structure and subsequent transcription. The loss of estrogen delivery once she discontinues the patch will result in the loss of estrogen receptor binding and activity at these genes. Histone deacetylase enzymes will then remove the acetyl groups on modified histones at these genes, resulting in reduced transcription.


A 44-year-old woman who emigrated from Poland three years earlier comes to your office with a chief complaint of fatigue of six months duration. A previous doctor told her she was anemic and had prescribed oral iron supplements, which she stopped taking because of the taste. Physical examination was unremarkable. During your conversation, she remarks that her mother had died from colon cancer at age 51, as did her maternal grandfather at age 55. Laboratory tests indicate she was indeed anemic, and a fecal occult blood test was positive. On a follow-up visit, colonoscopy and following pathologic examination of biopsied lesions resulted in the diagnosis of colon adenoma with villous features. Genetic testing indicated that the woman has a mutation resulting in a defect of a DNA repair pathway. Which of the following pathways is most likely dysfunctional in this patient?

A Homologous recombination repair

B Mismatch excision repair

C Nonhomologous end-joining repair

D Nucleotide excision repair

E Transcription coupled repair

B − The woman has a mutation in one of the genes necessary for mismatch excision repair (MER), resulting in hereditary nonpolyposis colorectal cancer. The familial history of colon cancer and the early onset of her disease are consistent with her diagnosis. The absence of MER results in the inability to repair nucleotide misincorporations that are not fixed during replication by the proofreading activity of DNA polymerase delta


A novel pharmaceutical agent in development claims to inhibit the activity of CDK2. The effect of this agent on the cell cycle should include

A inhibition of the G1/S transition

B maintenance of RB in a hyperphosphorylated state

C inhibition of the CDK inhibitor proteins p21 and p27

D promotion of the transcription of genes for cyclin E and cyclin A

A − Inhibition of the activity of CDK2 would prevent cells from exiting the G1 phase and thus entering the S phase.


You wish to clone the gene encoding a peptide hormone that will permit medical students to go without sleep while they are studying for their medical board examinations. You plan to express this gene in bacteria so that the hormone can be purified in commercial quantities. You have an antibody that recognizes the peptide hormone. What kind of recombinant DNA library will you screen?

A Genomic library cloned into a bacterial artificial chromosome (BAC) vector

B cDNA library cloned into an expression vector

C cDNA library cloned into the plasmid pBR322

D Genomic library cloned into a yeast artificial chromosome (YAC) vector

B − If you plan to identify a clone using an antibody, you must use an expression library that will produce the protein and then perform western blots on samples from each colony.


The mRNA sequence 5'-GCG ACG UCC-3', is being translated by a ribosome. Which of the following sequences represent the anticodons of the aminoacyl-tRNAs that were used (in order) during translation?

A 5'-UCC-3' 5'-ACG-3' 5'-GCG-3'

B 5'-GGA-3' 5'-CGU-3' 5'-GCG-3'

C 5'-GCG-3' 5'-ACG-3' 5'-UCC-3'

D 5'-CGC-3' 5'-CGU-3' 5'-GGA-3'

E 5'-CGC-3' 5'-GCA-3' 5'-UCC-3'

D − Codons and anticodons pair in an antiparallel manner forming a small double helix. If the mRNA has the sequence 5'-GCG ACG UCC-3', the first aminoacyl-tRNA anticodon would have the sequence 5'-CGC-3', to base pair with the mRNA. The second aminoacyl-tRNA anti-codon would be 5'-CGU-3'; the third anti-codon would be 5'-GGA-3'.


You carry out an experiment in which human brain RNA is analyzed via hybridization to a DNA probe. Which of the following best describes the hybridization technique used in this experiment?

A Western blotting
B Southern blotting
C Northern blotting
D DNA microarray

C − Northern blotting refers to a process by which RNA (immobilized on a membrane) is probed with a DNA molecule.