99:163 Medical Biochemistry Exam 2, Instructor-Dr. Wold October 9, 2009 Spivey & Watzke Auditoriums

During the Exam (8:30 - 10:20 am)

1. Select a seat leaving a space between individuals, turn off cell phones, leave backpacks and other personal belongings at front of auditorium.

2. Please fill in your student ID number (as well as your name) on the Scantron form and fill in the dots using a number 2 pencil. Extra pencils will be available.

3. You are welcome to use the bathroom during the exam. You must leave your personal belongings, the exam and the Scantron form in the exam room. Please let the instructor or TA know that you are leaving the room. We reserve the right to restrict the number of people leaving the room to one at a time.

4. If you believe you have detected a typographical error in a question, please ask the instructors about it during the exam. Any errors that are recognized will be corrected by placing a note on the chalkboard in each auditorium.

Suggestions for approaching multiple-choice questions.

1. Try to identify the best (rather than perfect) answer from the possible choices. 2. Think carefully about restrictive language such as all, some, never, always, etc. 3. Try to limit the choices and then guess (there is no penalty for incorrect answers).

After the Exam

1. If you finish prior to 10:20 am, please review your answers and quietly turn in your Scantron form to the instructor or TA.

2. Voices in the hallways travel and may be distracting to other students. Please wait until after all students are finished with the exam at 10:20 am before discussing it.

3. You are welcome to keep the packet of exam questions after you submit your Scantron form.

4. The Exam Key will be posted to the icon later in the day of the exam. 5. Prior to noon on Monday, October 12-

If you believe you have found an error in the Exam Key, please send a polite E-mail message to Dr. Wold (marc-wold@uiowa.edu). Please include Biochem Exam in the subject line, and indicate the relevant question(s) and foil(s) believed to be in error. If a correction is needed, the key will be modified to allow more than one answer to be counted as correct. Please note that I will not reply to your email right away. I will not make any decisions on changes to the key until I review all messages received by Monday.

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1. Which of the following statements about the eukaryotic cell cycle is true: a. DNA replication occurs in G1 phase. b. The G2/M transition is regulated by a checkpoint. c. DNA repair only occurs in S phase. d. RNA transcription occurs primarily in M phase. e. In dividing human cells, G0 follows S phase.

2. Which of the following statements is false about activation of a checkpoint in response to DNA damage?

a. RNA polymerase II encounters damage and terminates transcription. b. Sensor proteins bind to sites of DNA damage. c. Transducer kinases (ATM & ATR) are recruited to sites of DNA damage and

activated. d. Transducer kinases phosphorylate effector kinases. e. Effector kinases phosphorylate protein effectors to modulate cell cycle and DNA

repair. 3. Which of the following statements about DNA or RNA is false?

a. T base pairs with C b. purines base pair with pyrimidines c. G and A base pair with pyrimidines d. purines base pair with U or C e. A base pairs with U

4. Which of the following statements is true about triplex DNA (H-DNA)? a. Triplex DNA can form with any sequence of DNA b. Triplex DNA requires one strand be RNA c. Triplex DNA contains Hoogsteen base pairs d. Triplex DNA only are most stable at high pH where C is unprotonated e. Triplex DNA never forms in cells

5. Which of the following statements about histones is true? a. Histones are not well conserved in evolution. b. Winding of DNA around the histone octomer core of a nucleosome introduces

writhe into the DNA. c. Histones are basic proteins because they contain a high percentage of glutamine

and asparagine. d. The only posttranslational modification of histones is phosphorylation and

dephosphorylation. e. Histones have no role in packing DNA so it will fit in the nucleus.

6. A double strand break in DNA is required to initiate homologous recombination because: a. It will induce the G2-M checkpoint. b. It is required to provide a 3 end that can invade a homologous sequence. c. It provides a recognition site for telomerase. d. It causes a high rate of mutations that promote antibody diversity. e. It disrupts the structure of the chromatin at the site of recombination.

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7. Which of the following is not a similarity between homologous recombination and site-specific recombination?

a. Both processes have a 4-strand intermediate. b. Both processes require breaking and rejoining DNA strands. c. Both processes can change the sequence of the genome. d. Both processes occur in both prokaryotes and eukaryotes. e. Both processes can cause inversions or deletions of regions of the genome.

8. Which of the following statements about DNA replication enzymes is true. a. DNA polymerases have high processivity because they are covalently linked to

the template strand. b. At the replication fork, DNA helicases utilize energy from ATP hydrolysis to

translocate along the newly synthesized strand. c. Primases must add nucleotides to an existing a 3 OH group. d. Topoisomerases release the links between parental DNA strands. e. DNA ligases do not require a high-energy cofactor to form a phosphodiester

bond. 9. This week the 2009 Nobel Prize in Physiology was awarded to Elizabeth Blackburn,

Carol Greider and Jack Szostak for their discovery of telomerase. Which of the following statements about telomerase is true?

a. Telomerase acts at both telomeres and centromeres. b. Telomerase activates a checkpoint to prevent cell division if there is damage to

the telomere. c. Telomerase extends the 3 end of eukaryotic chromosomes to prevent

chromosome shortening. d. Telomerase expression decreases in most human cells that go through the

Hayflick limit and become transformed (cancerous). e. Telomerase acts at both the replication fork and at telomeres.

10. Two repair processes that are linked to DNA replication are mismatch repair and translesion synthesis (error prone repair). Which of the following statements about these repair processes is false?

a. Mutations in genes involved in mismatch repair can cause hereditary nonpolyposis colon cancer (HNPCC)

b. Translesion synthesis allows the replication fork to bypass damage that would otherwise cause the replication fork to stall.

c. Mismatch repair makes a transient gap in the newly synthesized strand to remove the mismatch.

d. Mismatch repair occurs in both prokaryotes and eukaryotes. e. Mutations in translesion synthesis proteins can cause Fanconis Anemia.

11. Why does DNA contain thymine instead of uracil? a. Because uracil wont hydrogen bond to adenine b. Because thymine is less sensitive to UV damage c. So that deamination of cytosine can be detected as a form of damage and be

repaired by base excision repair d. So that the deamination of cytosine can be detected as a form of damge and be

repaired by mismatch repair e. Because uracil induces kinks in helical structure of DNA

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12. Which of the following is the best statement describing types of chemical modifications of DNA?

a. Ultraviolet radiation in sunlight can cause interbase crosslinks between adjacent pyrimidine residues.

b. Chemical modification of DNA can alter base pairing. c. The glycosidic bond between deoxyribose and purine can spontaneously

hydrolyze in the aqueous environment in the nucleus. d. Reactive oxygen species produced by mitochrondria during electron transport can

modify either bases or the phosphodiester backbone of DNA. e. All of the above are true.

13. You are doing a research project on a novel, primitive unicellular eukaryote, called HKI. You find that this organism has a very small genome and contains only one RNA polymerase. This suggests that the process of transcription in this organism is more like prokaryotes than eukaryotes. If this is the case, which of the following statements is most likely to be correct about HKI transcription?

a. HKI RNA polymerase will have a C-terminal domain (CTD). b. HKI mRNA will be polyadenylated. c. HKI RNA polymerase will contain a 3 to 5 exonuclease used for proofreading. d. HKI RNA polymerase will terminate at sequences that contain a hairpin followed

by a string of A residues. e. HKI RNA polymerase does not need sigma factor to bind to

promoter/transcription start sites. 14. Which of the following techniques would be the best way to determine whether or not

the HKI genome contains introns? a. Use restriction endonucleases to make a map of the genome. b. Compare the sequences in a HKI genomic DNA library to those in a HKI cDNA

library. c. Isolate 20 fragments from an HKI genomic DNA library and use these fragments

to probe the restriction endonuclease digest of the full genome in a Southern blot. d. Use mass spectrometry to determine the protein sequence of 10 of the most

abundant proteins in HKI and compare the predicted gene sequences to similar sequences in other organisms.

e. Isolate mRNA from HKI, label the pool of mRNA and then determine the average size of the RNA using gel electrophoresis.

15. Assume that the results from the experiment described in the previous question demonstrates that HKI has introns and exons. Which of the follow statements is most likely to be true for HKI?

a. HKI will have small nuclear ribonuclear proteins (snRNPs). b. The length of the initial RNA transcripts in HKI will be shorter than the final

mRNA. c. The introns will act as primers during DNA replication. d. The introns will be cleaved by poly-A polymerase in HKI. e. The introns will be bound by a rho-like factor during splicing.

16. Which of the following proteins does not function primarily in the eukaryotic nucleus? a. RNA polymerase II b. RISC complex c. TATA binding protein d. Poly(A) polymerase e. DNA polymerase delta

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17. The first part of the sequence of the E. coli tryptophan operon mRNA is shown below.

Assume that you are analyzing an E. coli strain (X) that has a mutation in the tryptophan operator site so that the only regulation of this operon is by attenuation. You compare tryptophan mRNA levels in strain X to a mutated strain X that also has a mutation that changes the leucine codon* (CUG) in the leader peptide into a termination codon (UAG). Which statement best describes the expected change in mRNA levels that will be observed in the mutated strain?

a. Decrease levels of tryptophan mRNA under all growth conditions. b. Decrease levels of tryptophan mRNA under conditions of limiting tryptophan. c. Increase levels of tryptophan mRNA under all growth conditions. d. Increase levels of tryptophan mRNA under conditions of limiting tryptophan. e. Increase levels of tryptophan mRNA under conditions of abundant tryptophan.

18. Initiation of RNA polymerase II transcription requires all of the following except? a. TATA-binding protein (TBP) b. TFIIH c. Upstream regulatory sequences d. An open chromatin structure e. Dephosphorylation of the C-terminal domain of RNA polymerase II.

19. Which of the following is the best statement describing the general role of chromatin remodeling or functions of chromatin remodeling complexes?

a. Chromatin remodeling can cause the conversion of heterochromatin to euchromatin and vise versa.

b. Chromatin remodeling complexes primarily cause post-translational modifications on histone H1.

c. Chromatin remodeling complexes are usually small with a single enzymatic activity.

d. Euchromatin is the default state of human genome and heterochromatin is only present because of the constant action of chromatin remodeling complexes.

e. None of the above statements are true.

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20. Which of the following properties best describes most eukaryotic transactivating factors? a. They are only composed of a DNA binding domain and a protein interaction

domain. b. They primarily interact with modified histones in chromatin. c. They primarily interact with DNA, the basal transcription complex and co-

activators. d. They usually function independently of any other protein complexes. e. They primarily function by displacing repressors from the promoter region.

21. In class, we discussed a mutation in the DEC2 transcriptional repressor that was found in a family that seemed to need less sleep that normal. Transgenic mice carrying this mutant allele had a longer active cycle than control mice. A two channel microarray study is planned to try to determine which genes are expressed differently in the brains of mice carrying the mutant allele of DEC2. This experiment will start with RNA isolated from the brains of a control mouse and a DEC2 mutant mouse. The following statements describe steps in this experiment. Which step is incorrect or not appropriate?

a. The two RNA samples are used to make two cDNA pools. b. The two cDNA pools are labeled with different fluorescent labels. c. A mouse microarray is obtained that contains 32,000 probes complementary to

known mouse genes bound at defined locations on a large glass slide. d. Two samples are hybridized to separate mouse array slides and the level of

hybridization compared between the two slides. e. Analysis of the resulting data will provide the relative expression levels of all of

the genes on the array. 22. There are three codons in the standard genetic code that usually function to terminate

translation (UAA, UAG, UGA). Which of the following is false about terminator codons?

a. Mutations that change an amino acid codon into a termination codon are called missense mutations.

b. Terminator codons do not interact with standard tRNAs. c. An open reading frame is a sequence in DNA or RNA that does not contain any

terminator codons. d. In humans, a rare specialized serine tRNA incorporates selenocysteine at some

UGA codons. e. Mitochondria in some organisms use a non standard codon to terminate

translation. 23. Aminoacyl-tRNA synthetases are important for charging tRNA with the proper amino

acids. Which of the following statements about aminoacyl-tRNA synthetases is true? a. The energy used by aminoacyl-tRNA synthetases to couple an amino acid to a

tRNA comes from hydrolysis of two molecules of GTP. b. One major source of specificity of the charging reaction comes from binding the

proper amino acid. c. Aminoacyl-tRNA synthetases recognize the correct tRNA by interacting with the

anticodon. d. Aminoacyl-tRNA synthetases are part of the ribosome. e. None of the known aminoacyl-tRNA synthetases have editing or proofreading

activity to increase the accuracy of charging.

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24. Which of the following statements describes a similarity between initiation of protein synthesis in prokaryotes and eukaryotes by ribosomes?

a. Both usually initiate at multiple different start codons on a message. b. Both do not require any high-energy cofactors (e.g. ATP, GTP) for initiation. c. In both an assembly of the large and small ribosome subunits binds to the mRNA. d. Both use AUG as a start codon. e. Binding of the mRNA to the ribosome is directed by base pairing between a

ribosomal RNA and a specific sequence in the mRNA. 25. Which of the following statements about peptide bond formation on the ribosome is

true? a. The ribosome only requires mRNA, aminoacyl-tRNAs and nucleotide cofactors

(GTP & ATP) to form a new peptide bond. b. The nascent polypeptide chain is bound to the A site while the next incoming

aminoacyl-tRNA binds to the P site. c. Specificity of the incoming aminoacyl-tRNA is regulated by a two-step binding

reaction and requires GTP hydrolysis. d. The ribosome proofreads each aminoacyl-tRNA to make sure the proper amino

acid is attached before synthesizing a peptide bond. e. None of the other four answers are correct.

26. Which of the following statements is true about protein folding? a. Proteins predominantly fold after detaching from the ribosome. b. Because the information needed for folding is in the primary sequence, all

proteins fold correctly by themselves. c. Protein folding only occurs in the cytoplasm. d. The final folded structure of a protein determines to which part of the cell (which

organelle) it is transported. e. Molecular chaperones require ATP hydrolysis to promote proteins folding into

their native structure. 27. Pick the best answer for this sentence: DNA sequencing

a. is used in DNA fingerprinting. b. requires the experimenter to know the source of the DNA. c. methodology will work equally well on RNA and DNA. d. is usually automated and highly efficient. e. always requires separating the DNA on by gel elecrophoresis.

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Answer Key Exam #2 - 99:163 2009

1. B 2. A 3. A 4. C 5. B 6. B 7. E

8. D 9. C 10. E 11. C 12. E 13. D 14. B

15. A 16. B 17. E 18. E 19. A 20. C 21. D

22. A 23. B 24. D 25. C 26. E 27. D

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Practice Questions for Medical Biochemistry Wold Lectures - September, 2010

1. Which of the following is usually NOT a constituent of DNA a. phosphate (PO4) b. the purine Guanine c. the pyrimidine Uracil d. the purine Adenine e. deoxyribose

2. Twist is best described by: a. The rotation of a base relative to the orientation of the deoxyribose in degrees b. The number of times the two strands pass around each other in the DNA helix. c. The number of times the two strands pass around each other in three-

dimensional space. d. The total number of times the two strands pass around each other. e. The mobility of the DNA in agarose gel electrophoresis

3. B-form DNA a. is unaffected by pH. b. has a major and a minor groove. c. can form with one RNA and one DNA strand. d. always has writhe. e. All of the above.

4. The action of a eukaryotic type II topoisomerase on a negatively supercoiled DNA molecule causes

a. the linking number to change by multiples of 1. b. a transient break in one DNA strand. c. unwinding of the B-form DNA. d. a change in the writhe of the DNA molecule. e. All of the above

5. Which of the following properties is NOT true of histones? a. Histones form a dodecamer complex that binds DNA non-specifically. b. Histones have an amino acid content that includes a high proportion of lysine

and arginine. c. Histones are the core components of the nucleosome d. Histone get modified after translation on both N- and C-terminal tails e. Histone modifications can regulate gene transcription

6. Which of the following statements about replication proteins is FALSE? a. DNA polymerases require a primer for synthesis. b. DNA helicases translocate along ssDNA and separate the two strands in the

helix. c. Single-stranded DNA binding proteins prevent secondary structure in ssDNA. d. Sliding clamp proteins stabilize the protein complex at the origin of replication

until priming can occur. e. DNA ligase is important in the processing of Okazaki fragments.

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7. DIFFERENT mechanism in prokaryotic and eukaryotic DNA replication. a. Okazaki fragment processing b. Processivity of replicative DNA polymerases c. Primer synthesis for Okazaki fragments d. Regulation of initiation of replication at origins on chromosomes. e. Separation of the parental DNA strands at the replication fork

8. Conversion of DNA damage to a mutation REQUIRES: a. the modification to break the DNA strand. b. DNA replication of the modified base. c. the modification to not be recognized by the cellular repair machinery. d. the modification to be recognized by the cellular repair machinery. e. the cellular check points to be disrupted.

9. Which of the following definitions is the most precise description of double-strand break repair via homologous end-joining?

a. A repair pathway that fixes errors that occur during DNA replication. b. A repair pathway that fixes errors with some loss of genetic information. c. DNA repair that only occurs after S-phase. d. General recombination with the break resulting from DNA damage. e. A repair pathway in which proteins including Ku and DNA protein kinase

(DNA-PK) bind DNA ends and then promote ligation to recreate a continuous DNA strand.

10. The human genome contains which of the following classes of DNA sequence: a. Exons b. Sines c. Lines d. Retrotransposons e. All are found in the human genome

11. Which of the following is NOT a common property of E. coli RNA polymerase? a. RNA polymerase synthesizes RNA in a 5 to 3 direction. b. RNA polymerase transiently unwinds the DNA. c. RNA polymerase binds a sigma factor to initiate transcription. d. RNA polymerase can usually transcribe either either a DNA or an RNA

template. e. RNA polymerase can initiate synthesis without a primer.

12. Eukaryotic RNA polymerase II has a C-terminal domain (CTD) that is involved in a number of processes in transcription. Which of the following is NOT TRUE for the CTD?

a. It interacts with the polyadenylation complex. b. It interacts with the complex that adds the cap to the 5 end of the RNA

transcript. c. It interacts with the spliceosome through snRNPs. d. It interacts with transcription mediator complexes. e. It interacts with the DNA at the promoter.

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13. snRNAs in eukaryotic cells

a. provide the purine that carries out the initial nucleophilic attack during the splicing of RNA polymerase II transcripts.

b. recognize the splice junctions during splicing of RNA polymerase II transcripts. c. hydrolyze ATP during splicing. d. interact with tRNAs during translation. e. can function without proteins.

14. HIV differs from most other retroviruses because a. it kills the cells it infects. b. it has a reverse transcriptase that does not have a 3 to 5 proof-reading

exonuclease. c. it initially expresses its viral proteins as a polyprotein. d. it passes through a double stranded DNA intermediate. e. its replication is inhibited by nucleotide analogues.

15. Which of the following regulatory motifs or proteins DO NOT bind to DNA? If a motif is specified, consider the function of the motif only.

a. Leucine zipper motif b. Helix-turn-helix motif c. Lac repressor d. Zinc-finger proteins e. Catabolite activator protein (CAP)/cAMP repressor proteins (CRP)

16. Chromatin remodeling a. opens up the structure to allow DNA binding proteins to bind to target sites. b. is caused by changes in the modifications on histone tails. c. is catalyzed by the Swi/snf complex. d. results in a stable chromatin structure. e. all of the above.

17. Which of the following steps does NOT occur in activation of a majority of genes in eukaryotic cells?

a. Binding of TATA-binding protein (TBP) to a TATA sequence. b. Interaction of mediator complexes with the basal transcription machinery. c. Small molecules/metabolites interaction with protein repressors causing reduced

binding to UAS sequences. d. Transactivators binding to the DNA near the promoter. e. DNA looping allows distant sites to act on the promoter.

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18. Gal4 protein is a transactivator from yeast that activates the expression of genes involved in

galactose metabolism. Gal4 is composed of a zinc-finger domain, a coiled-coil domain and an acidic activator domain. Suppose a yeast strain was created that did not contain wild-type Gal4 protein but instead had a recombinant Gal4 protein in which the Gal4 activator domain was replaced with the acidic activation domain of GCN4. (GCN4 is a yeast transcriptional activator protein that stimulates the expression of genes involved in amino acid biosynthesis and is induced by amino acid starvation.) Predict what would happen to the expression of the two classes of genes listed in the table if this strain is grown in media with galactose. (In the table: = no induction, ++ = induction, + = weak induction.)

Galactose metabolism genes

Amino acid biosynthesis genes

a. b. ++ c. + d. ++ ++ e. None of the above

19. Wobble base-pairing refers to a. degeneracy in the genetic code. b. a mechanism by which some tRNA synthetases can charge several related tRNA

molecules. c. the property by which a single tRNA anticodon can interact with several

different related codons. d. the mechanism by which a mutant suppressor tRNA can bind and cause the

insertion of an amino acid at a termination codon. e. alternate base pairing found in triplex DNA.

20. In transcriptional attenuation that occurs in the Tryptophan operon, a. translation regulates the rate of transcription termination. b. transcription regulates the rate of translation termination. c. transcription undergoes a frame shift to allow the expression of certain genes. d. pauses in translation regulate mRNA degradation. e. pauses in transcription allow rho dependent termination.

21. Which of the following processes do NOT contribute to the overall accuracy of translation? a. Amino acid coupling to tRNA by aminoacyl-tRNA synthetases. b. Editing (hydrolase) activity in aminoacyl-tRNA synthetases. c. Recognition of the tRNA by aminoacyl-tRNA synthetases. d. Binding of the aminoacyl-tRNA to the A site of the ribosome. e. Peptide bond formation by peptidyl transferase in the ribosome.

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22. Which of the following statements is true?

a. Proteins usually fold completely before they are transported to the lumen of the Endoplasmic Reticulum.

b. Some neurological diseases are caused by accumulation of aberrantly folded proteins.

c. All proteins require molecular chaperones for proper folding. d. Ubiquitin binds to unfolded proteins and targets them for degradation. e. Glycosylation of proteins occurs in the cytoplasm.

23. Which of the following techniques would not be used in one or both of the types of DNA

fingerprinting? a. DNA sequencing b. Restriction endonuclease cleavage c. Southern blotting d. PCR amplification e. Gel electrophoresis

24. Which of the following statements is NOT true? a. Type II restriction endonucleases cut DNA at specific sequences. b. Type II restriction endonucleases are a useful tool for cloning DNA sequences. c. Type II restriction endonucleases can be used to make a genomic DNA library. d. Type II restriction endonucleases usually cut methylated DNA. e. Type II restriction endonucleases can produce DNA ends with short single

stranded overhangs. 25. DNA microarrays

a. can determine the stability of thousands of RNAs in a cell at the same time. b. rely on northern (RNA:DNA) hybridization. c. compare two different samples from cells or tissues. d. can usually be analyzed by visual inspection. e. can be used to determine the changes in the genome of a specific tumor.

26. hich of the following classes of proteins can contribute to the development of cancer? a. Growth factors b. Signal-transduction proteins c. DNA repair proteins d. Transcription factors e. All of the above

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27. In the Watson-Crick model for the DNA double helix (B form) the AT and GC base pairs

share which one of the following properties? a. The distance between the two glycosydic (base-sugar) bonds is the same in both

base pairs, within a few tenths of an angstrom. b. The molecular weights of the two base pairs are identical. c. The same number of hydrogen bonds is formed between the two bases of each

pair. d. The plane of neither base pair is perpendicular to the axis of the helix. e. The proton-binding groups in both base pairs are in the charged or ionized form.

28. The action of a type I topoisomerase on a negatively supercoiled DNA molecule causes a. Changes in the linking number of a DNA molecule b. A transient break in one DNA strand c. Changes in the Writhe of the DNA d. The DNA to become relaxed e. All of the above

29. Which of the following processes contribute to the compaction of DNA in a eukaryotic cell? a. DNA binding to histones b. Arrangement of histones into 30 nm fibers c. Attachment of the DNA to a chromosomal scaffold d. Post translational modification of nucleosomes e. All of the above

30. An Okazaki fragment is a: a. fragment of DNA resulting from endonuclease action. b. fragment of RNA that is a subunit of the 30S ribosome. c. piece of DNA that is synthesized in the 3' ! 5' direction. d. segment of DNA that is an intermediate in the synthesis of the lagging strand. e. segment of mRNA synthesized by RNA polymerase.

31. At replication forks in E. coli: a. DNA helicases make endonucleolytic cuts in DNA. b. DNA primers are degraded by exonucleases. c. DNA topoisomerases make endonucleolytic cuts in DNA. d. RNA primers are removed by primase. e. RNA primers are synthesized by primase.

32. Which of the follow DNA repair pathways only corrects errors that occur during S-phase? a. Mismatch repair b. Nucleotide Excision Repair c. Base Excision Repair d. Direct reversal of damage by O6-methlyguanine DNA methyltransferase e. Nonhomologous End Joining

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33. Unlike bacteria, eukaryotic chromosomes need multiple DNA replication origins because:

a. eukaryotic chromosomes cannot usually replicate bidirectionally. b. eukaryotic genomes are not usually circular, like the bacterial chromosome is. c. the processivity of the eukaryotic DNA polymerase is much less than bacterial

enzyme. d. their replication rate is much slower, and it would take too long with only a

single origin per chromosome. e. they have a variety of DNA polymerases for different purposes, and need a

corresponding variety of replication origins. 34. .When bacterial DNA replication introduces a mismatch in a double-stranded DNA, the

methyl-directed repair system: a. cannot distinguish the template strand from the newly replicated strand. b. changes both the template strand and the newly replicated strand. c. corrects the DNA strand that is methylated. d. corrects the mismatch by changing the newly replicated strand. e. corrects the mismatch by changing the template strand.

35. In base-excision repair, the first enzyme to act is: a. AP endonuclease. b. Dam methylase. c. DNA glycosylase. d. DNA ligase. e. DNA polymerase.

36. Which of the following statements about site-specific recombination is not true? a. Site-specific recombination is catalyzed by enzymes called recombinases and/or

transposases b. Site-specific recombination is necessary for generating antibody diversity in

mammals c. Site-specific recombination can cause insertion or deletion of DNA sequences d. Site-specific recombination can cause inversion of DNA sequences e. Site-specific recombination initiates with a double strand break in DNA

37. Which of the following statements about genes is true: a. A gene can direct the synthesis of a protein or a RNA. b. Genes are continuous DNA sequences. c. All sequences in the genome that contain genetic information are genes. d. The structure of genes is the same in prokaryotes and eukarotes e. The number of genes in an organism correlates with the size of its genome.

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38. Which one of the following is true about the genetic code?

a. All codons recognized by a given tRNA encode different amino acids. b. It is absolutely identical in all living things. c. Several different codons may encode the same amino acid. d. The base in the middle position of the tRNA anticodon sometimes permits

wobble base pairing with 2 or 3 different codons. e. The first position of the tRNA anticodon is always adenosine.

39. RNA polymerase: a. binds tightly to a region of DNA thousands of base pairs away from the DNA to

be transcribed. b. can synthesize RNA chains de novo (without a primer). c. has a subunit called " (lambda), which acts as a proofreading ribonuclease. d. separates DNA strands throughout a long region of DNA (up to thousands of

base pairs), then copies one of them. e. synthesizes RNA chains in the 3' ! 5' direction.

40. Splicing of introns in eukaryotic nuclear mRNA primary transcripts requires: a. a guanine nucleoside or nucleotide. b. endoribonucleases. c. polynucleotide phosphorylase. d. RNA polymerase II. e. small nuclear ribonucleoproteins (snurps).

41. Which of the following DNA sequences is not generally required for initiation of transcription in eukaryotes.

a. TATA box b. Up-element c. Upstream activator sites d. Enhancers e. Inr sequence

42. Which of the following enzymes does not belong: a. DNA Polymerase delta b. Telomerase c. HIV reverse transcriptase d. RNA polyerase II e. DNA polymerase lambda

43. Which of the following best describes splicing of RNA polymerase II transcripts a. Splicing initiates when a 2OH from an andenosine attacks the 5splice site b. A proteins in the spliceosome contains the active site to catalyze splicing c. Splicing rearranges genes to simplify RNA transcripts d. Splicing does not require energy because all the reactions are exchange

reactions e. Splicing can occur without proteins.

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44. Small signal molecules (like cAMP in the lac operon) can do which of the following in regulating bacterial gene expression:

a. provide input to the regulatory process that depends on the nutritional/energy status of the cell

b. increase repressor binding to operator sites c. reduce repressor binding to operator sites d. increase activator binding to its binding site e. all of the above

45. Which of the following eukaryotic complexes/proteins is most likely to cause global changes in the regulation of gene expression?

a. An enhancer binding protein b. The concentration of a basal transcription factor c. A chromatin remodeling complex d. A general transcriptional mediator e. A transcriptional repressor

46. Which of the following processing events does not occur with tRNAs in eukaryotic cells? a. Cleavage of the 3 terminus b. CAP addition to the 5 terminus c. Methylation of some bases d. Deamination of some bases e. Splicing of intron(s)

47. Complete the following sentence: The genetic code a. has one start codon and two stop codons b. is universal in all organisms on earth c. is not degenerate d. allows a single sequence to have encode multiple genes e. has variable word length

48. Pick the best ending of the following sentence: In initiation of translation in eukaryotes a. the small ribosome subunit initially binds to the first AUG in the mRNA b. only GTP is hydrolyzed c. uses a specialized tRNA d. assembles the two subunits of the ribosome before binding tRNA e. binds the initiator tRNA in the A-site

49. Pick the statement that is NOT CORRECT about the Polymerase Chain Reaction (PCR). a. PCR amplifies DNA segments geometrically b. PCR is usually done using heat stable DNA polymerases c. PCR requires two primers that are complementary to the ends of the target DNA d. PCR can synthesize DNA with high fidelity e. PCR requires DNA ligase

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50. Which of the following statements is FALSE about Molecular chaperones?

a. Molecular chaperones mostly function during heat shock conditions. b. Molecular chaperones require ATP hydrolysis to function c. Molecular chaperones help some proteins fold as they are being synthesized d. Molecular chaperones help some proteins refold after they are denatured e. Molecular chaperones interact with unfolded regions on proteins

51. Cyclin-dependent kinases play a critical role in regulating the cell cycle. As such they are subjected to multiple levels of regulation. Which of the following is NOT a mechanism that human cells use to regulate cyclin-dependent kinases?

a. Modulation of the cellular levels of cyclins. b. Phosphorylation of the cyclin-dependent kinase. c. Regulation of the synthesis of cyclin-dependent kinases by growth factors. d. Binding of GTP to an allosteric site on the kinase. e. Binding of protein inhibitors to the cyclin-cdk complex.

52. Cancer is a family of diseases that are characterized by abnormal cell proliferation. Which of the following statements BEST describes a property of cancer cells?

a. Cancer cells have normal cellular checkpoint activation. b. Cancer development requires mutation of both copies of a proto-oncogene to an

activated form. c. Cancer is usually derived from a single cell that has multiple mutations. d. Cancer will only occur if an individual inherited at least one copy of a mutant

allele of a tumor suppressor gene. e. Cancer occurs when cells fuse abnormally.

53. ene X encodes a functional transcriptional regulator (protein X) that increases p21 protein levels in cells. What is the LIKELY effect of constitutively increasing gene X expression in cancerous tissue within patients who suffer from Li-Fraumeni cancer syndrome? (Patients with this syndrome inherited one defective allele of p53 from a parent.)

a. No effect since p53 is already mutated in this syndrome. b. There will be increased activation of the G1 checkpoint. c. There will be decreased activation of the G1 checkpoint. d. The effect of the p53 mutation will be enhanced; the cancer will become

metastatic. e. There will be a decrease in the stability of p21 protein.

54. Experiments are done to understand the mechanism by which protein X regulates the expression of p21. Which of the following statements is LEAST LIKELY to describe a possible mechanism by which protein X is activating p21 transcription.

a. Protein X is a ribosomal protein. b. Protein X modulates the activity of the SWI/SNF complex. c. Protein X binds the coactivator complex, Mediator. d. Protein X requires zinc ions to function. e. Protein X binds to a specific class of enhancer.

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55. There is a cell line in which gene X has been knocked out using cre/lox gene replacement. mRNA from the knock-out cells and from the parental line (with intact gene X) are isolated and subjected to microarray analysis to try to understand the effect(s) of protein X on gene expression. Which of the following statements is FALSE about this experiment?

a. cDNAs are made from both mRNA samples and each sample is labeled with a different fluorescent tag linked to a dNTP.

b. The microarray contains thousands DNA sequences from human genes. c. The two samples are hybridized to the DNA microarray. d. After quantitation, the absolute number of RNA molecules present in the

knockout cells is determined for all of the DNA sequences in the microarray. e. Computerized analysis will be required to determine which of the differences

observed are significant. 56. Base pairing of nucleic acids is critical for many processes in cells and in the laboratory.

Which of the following statements about base pairing is FALSE? a. G-C and A-T base pairs have similar geometry. b. G-C and A-T base pairs have similar thermal stability. c. Base pairing is important for formation of tertiary structure in tRNA and rRNA. d. Base pairing directs the specificity of RNA silencing by microRNAs. e. Base pairing occurs in the formation of triplex DNA.

57. Which of the following is CORRECT regarding LINES, SINES, and retroviruses? a. LINES and SINES are thought to be derived from retroviruses. b. LINES and SINES may produce active viral particles whereas integrated

retroviruses do not. c. LINES, SINES, and retroviruses all have open reading frames (ORFs). d. LINES and SINES are found exclusively in genes whereas retroviruses randomly

integrate into the genome. e. LINES, SINES, and retroviruses occur rarely in the genome.

58. Which of the following is FALSE regarding DNA topology? a. Linking number (L) cannot change unless DNA strands are broken. b. B-form DNA has +1 twist (T) for every 10.4 base pairs. c. DNA with a writhe (W) of zero is termed relaxed. d. Binding of DNA to histones in the presence of a type I topoisomerase changes the

writhe (W) of DNA. e. Cruciform DNA preferentially forms upon overwinding the DNA.

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59. DNA replication requires the concerted action of multiple proteins to accurately duplicate genomic DNA. Which of the following statements about DNA replication in eukaryotes is TRUE?

a. DNA replication initiates at a single unique site on each chromosome. b. The accuracy of DNA synthesis by classical DNA polymerases is the only

mechanism for ensuring that DNA replication is accurate. c. It is necessary for a clamp-loading complex to topologically link the sliding

clamp, PCNA, to the DNA to make the replicative DNA polymerase highly processive.

d. RNA primers are removed by base excision repair after the lagging strand has been ligated to form a continuous strand.

e. Initiation of eukaryotic replication is regulated by (i) cyclin-dependent kinases (cell cycle dependent kinases) and (ii) protein complexes forming at sites of initiation but (iii) not by degradation of initiation proteins.

60. Which of the following MOST ACCURATELY describes the function of a type I topoisomerase?

a. Can link (catenate) or unlink (decatenate) two DNA molecules. b. Changes linking number (L) in units of 2. c. Has a catalytic mechanism that causes a transient break in one strand of DNA. d. Function only on positively supercoiled DNA. e. Is directly affected by the mutation that causes Li-Fraumeni cancer syndrome.

61. A patient presents with a large, darkly colored, irregularly shaped skin blemish on her shoulder. The patient sunbathes extensively in the summer and used tanning salons during the winter. Upon thinking back to Medical Biochemistry, you remember that thymidine dimers are commonly formed by excess exposure to UV light. Which of the following is TRUE regarding thymidine dimers?

a. They form as cyclobutane rings between the two consecutive purine bases. b. Fixing this type of DNA damage requires recombinational repair. c. Nucleotide excision repair would be unlikely to help fix this type of DNA

damage. d. This type of DNA damage is repaired less efficiently in patients with Xeroderma

Pigmentosum. e. DNA ligase is not required to fix this type of DNA damage.

62. Which of the following definitions is the MOST PRECISE description of double strand break repair via recombinational repair?

a. A repair pathway that directly rejoins the broken DNA with some loss of genetic information at the site of the break.

b. A repair pathway that only occurs during DNA replication c. A repair pathway in which a Holliday junction is formed between the broken

DNA and a homologous DNA molecule. d. A repair pathway in which the damage is removed by a specific glycosylase. e. A repair pathway that requires the action of a translesion DNA polymerase.

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63. Which of the following is FALSE regarding V-J recombination?

a. Some DNA is permanently lost in these cells. b. Transesterification catalyzed by an internal A residue causes the loss of the

intervening DNA segments. c. The reaction is error-prone. d. The function is to maximize immunologic recognition of diverse foreign

molecules. e. V-J recombination is essential for normal immune function.

64. While doing scientific research during the summer between your M1 and M2 year of medical school, you decide to pulse-label some living human cells with radioactive uridine triphosphate. You fractionate the different types of nucleic acid from these cells. Which of the following fractions will have the MOST radioactivity?

a. Ribosomal RNA b. Messenger RNA c. Transfer RNA d. Genomic DNA e. Mitochondrial DNA

65. Which of the following statements describing genomic libraries and library screening is FALSE?

a. A genomic library is usually made by digesting genomic DNA with a restriction endonuclease.

b. A genomic library will contain both exon and intron sequences. c. The library can be screened using colony hybridization d. A synthetic oligonucleotide to a known gene sequence can be used to screen the

library. e. It is only possible to screen a library for a gene using a probe that is

complementary to the template strand of that gene. 66. Which of the following statements is TRUE about bacterial RNA polymerase?

a. Binding of the RNA polymerase to a promoter is mediated by the sigma subunit binding to the UP element.

b. RNA polymerase synthesizes an RNA transcript that has an identical sequence to the template strand (except for U substituting for T).

c. RNA polymerase synthesizes RNA in a 5 to 3 direction from a DNA template and requires a primer.

d. RNA polymerase synthesizes an RNA transcript that is complementary to the coding strand.

e. Initially forms an inactive complex on the DNA called a closed complex. Which of the following statements is the MOST ACCURATE comparison of initiation of

prokaryotic RNA polymerase (RNAP) and eukaryotic RNA polymerase II (Pol II)? a. RNAP initiates at specific sites called promoters while Pol II does not initiate at

specific sites. b. Both RNAP and Pol II initiate at specific sites called promoters and only Pol II

undergoes a conformational change from closed to open conformation prior to initiation of transcription.

c. RNAP binds to promoters in the absence of any cofactors other than a sigma subunit while Pol II requires the action of multiple and often diverse factors to form a stable complex at a promoter.

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d. RNAP always requires the rho (#) factor to terminate transcription at a specific sequence while Pol II does not terminate at specific sites.

e. Both RNAP and Pol II have a repeated amino acid sequence at the C-terminus of the catalytic subunit that is phosphorylated and used to regulate activity.

68. Primary transcripts of eukaryotic nuclear mRNA are spliced and modified after transcription and before translation. Which of the following is FALSE about splicing?

a. Splicing can be different in different tissues. b. Splicing of mRNA primary transcripts requires multiple snRNAs (small nuclear

RNAs). c. Alternate splicing can occur in the same cell type. d. ATP hydrolysis does not appear to be required for the RNA cleavage or ligation

steps in the spliceosome. e. Messenger RNAs are the only type of RNAs that have introns and are spliced.

69. Chromatin structure is very important in regulating gene expression patterns. Which of the following is TRUE of chromatin?

a. Histone acetylation and phosphorylation are not reversible. b. Histone deacetylases repress transcriptional activity. c. Chromatin remodeling is usually a spontaneous process (does not require ATP). d. Histone modifications most commonly occur on histone H1. e. Histones are small, hydrophobic proteins.

70. Transcription in eukaryotes is largely regulated by positive transcriptional regulators, including a number of leucine zipper proteins. Which of the following is NOT characteristic of leucine zipper proteins?

a. Dimerize via an aliphatic interface rich in leucine residues b. Bind DNA by forming a sliding clamp around the nucleotide backbone c. Can form either homo- or heterodimers d. Both proteins in a dimer interact with DNA. e. Activate transcription by affecting binding or activity of RNA polymerase II.

71. Which of the following is FALSE about the genetic code? a. A missense mutation changes the sequence of the DNA and the amino acid

encoded by the DNA. b. An open reading frame is a series of codons without stop codons. c. A silent mutation changes the sequence of the DNA without changing the amino

acid sequence encoded by the DNA. d. All DNA in the human body uses exactly the same genetic code. e. Translation of homoribopolymers results in homopolypeptides.

72. Transcription and translation are coupled in prokaryotes. Which of the following statements is FALSE about prokaryotic transcription and translation?

a. Prokaryotic transcription is often regulated by repressors binding to operators and blocking RNA polymerase binding.

b. In the tryptophane operon the cellular level of tryptophane charged aminoacyl tRNA helps regulate tryptophane mRNA levels.

c. A mRNA molecule has only one ribosome bound and translating protein at a time. d. Prokaryotic translation initiates by an interaction between the 16S ribosomal RNA

and a specific sequence in the message just up-stream from the AUG. e. Prokaryotic mRNA can contain multiple open reading frames (i.e. is

polycistronic).

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73. Peptide bond formation occurs in the ribosome. Which of the following statements is TRUE?

a. The ribosome only requires mRNA, aminoacyl-tRNAs and nucleotide cofactors (GTP & ATP) to form a new peptide bond.

b. The nascent polypeptide chain is bound to the P site while the next incoming aminoacyl-tRNA binds to the A site.

c. Specificity of the incoming aminoacyl-tRNA is regulated by a two-step binding reaction and requires GTP hydrolysis. This is the only GTP hydrolyzed during the synthesis of a peptide bond

d. The ribosome proofreads each aminoacyl-tRNA to make sure the proper amino acid is attached before synthesizing a peptide bond.

e. None of the other four answers are correct. 74. molecular techniques are listed with a molecule or reaction that is important in that

technique. Choose the INCORRECTLY matched pair. a. Sanger DNA sequencing, dideoxynucleoside triphosphates b. DNA fingerprinting, variable number tandem repeat sequences (VNTRs) c. Cloning DNA fragments, DNA ligase d. PCR, extension from a 3 phosphate e. Restriction endonuclease digestion, sequence-specific DNA-cleavage reaction

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75. A short fragment of protein X (discussed in questions

53-55), has a partial amino acid sequence determined by multidimensional mass spectrometry. Two polypeptides are determined: Fragment L (Met-Lys-Tyr-Cys-Ile-Asn) and Fragment P (Ser-Arg-Leu-Cys-Gly-Pro). Using your knowledge of the structures of the amino acids, translation and the genetic code (shown at right), which of the following statements is CORRECT regarding the two fragments?

a. The potential coding sequences for Fragment L are less degenerate than those for Fragment P.

b. The potential coding sequences for Fragment P are less degenerate than those for Fragment L.

c. At pH 7, Fragment P is more positively charged than Fragment L.

d. At pH 7, Fragment L is more positively charged than Fragment P.

e. Fragment P is more likely to be a signal peptide than is Fragment L. 76. Which of the following statements is true about protein synthesis?

a. All proteins fold properly during translation. b. RNA editing can cause premature termination of translation by changing an

amino acid codon to a stop codon. c. A frameshift that occurs during translation always results in premature

termination of the polypeptide chain. d. Proteins destined to be localized within the plasma membrane are synthesized in

the Golgi complex. e. Poly-ubiquitination of proteins (addition of multiple ubiquitin molecules to lysine

residues on the protein) targets the protein for extra-cellular secretion. 77. A human gene (G) is discovered that, when expressed, directly blocks production of

protein Z from gene Y. Which of the following is LEAST LIKELY be true for gene G? a. Gene G may encode a reverse transcriptase. b. Gene G may affect the production of protein from RNA. c. Gene G may not encode for a protein. d. Gene G may encode a transcriptional repressor that interacts with gene Y. e. RNA from gene G may interact with the RISC complex.

Practice Questions for Medical Biochemistry Wold Lectures

September, 2010

Answer Key 1. C 2. B 3. B 4. D 5. A 6. D 7. D 8. B 9. D 10. E 11. D 12. E 13. B 14. A 15. A 16. E 17. C 18. B 19. C 20. A 21. E

22. B 23. A 24. D 25. C 26. E 27. A 28. E 29. E 30. D 31. E 32. A 33. D 34. D 35. C 36. E 37. B 38. C 39. B 40. E 41. B 42. D

43. A 44. E 45. C 46. B 47. D 48. C 49. E 50. A 51. D 52. C 53. B 54. A 55. D 56. B 57. A 58. E 59. C 60. C 61. D 62. C 63. B

64. A 65. E 66. E 67. C 68. E 69. B 70. B 71. D 72. C 73. B 74. D 75. A 76. B 77. A