BIO360 Fall 2013 Quiz 1

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1 BIO360 Fall 2013 Quiz 1 1. Examine the diagram below. There are two homologous copies of chromosome one and the allele of YFG carried on the light gray chromosome has undergone a loss-of-function mutation. If a mitotic recombination event occurs (as shown below), two different sets of daughter cells are possible. Diagram chromosome 1 in the four possible cells and put a star next to those which show a loss-of-heterozygosity. (4 points) and and 2. The Warburg Effect refers to the phenotype that cancer cells (2 points) A. have been transformed by a retrovirus. B. effectively resist being killed by the immune system. C. are resistant to death by apoptosis. D. primarily use anaerobic cell respiration. E. are capable of anchorage-independent growth. 3. Which of the following is not and example of an epigenetic modification? (2 points) A. Histone methylation B. Histone acetylation C. Substitution mutation of a G to an A D. Methylation of a GC dinucleotide 4. All stem cells share what two characteristics? (2 points)

2 BIO360 Quiz 2 September Imagine that the p21 gene (which encodes a CDK inhibitor) has been transcriptionally silenced due to extensive methylation upstream of the gene and that this modification is contributing to the transformation of the cell. Which of the follow terms would apply to p21? Circle all that apply. (2 points) Aneuploid Caretaker Epi-Driver Indel Mut-Driver Oncogene Passenger Protooncogene Tumor Suppressor Gene 2. Name that term. (2 points each) Two genes from different organisms that share an evolutionary history and carry out the same function. All of the DNA which is transcribed and retained after splicing. The point in the cell cycle after which growth factors are no longer needed for cycling to occur. 3. In one sentence or less, what is the appropriate conclusion for Figure 4C from the Zhang et al paper? (2 points)

3 BIO360 Quiz 3 October 7 1. What protein deactivates Ras protein? (2 points; standard abbreviation is fine) 2. In class, we said that Elk-1 is a transcription factor that moves to the nucleus when it gets phosphorylated by ERK. When it is in the nucleus, it activates the transcription of the DHFR gene. Imagine the following experiment: We create a mutant Elk-1 which adds a Nuclear Export Signal to the protein so that it is never located in the nucleus. We find that DHFR is never transcribed under these conditions, regardless of ERK activity. This experiment demonstrates that Nuclear localization is necessary for Elk-1 to activate transcription of DHFR. Nuclear localization is sufficient for Elk-1 to activate transcription of DHFR. Nuclear localization is both necessary and sufficient for Elk-1 to activate transcription of DHFR. Nuclear localization is neither necessary nor sufficient for Elk-1 to activate transcription of DHFR. Please circle your answer and then briefly explain your logic below. (2 points) 3. Which one statement correctly describes the Myc protein? (2 points) A. Only Myc-Max heterodimers can bind to the enhancer. B. The G12V mutation of Myc is commonly found in human tumors. C. Phosphorylated Myc has a shorter half-life than dephosphorylated Myc. D. Max-Max homodimers bind to the enhancer and repress transcription. E. Dimerization happens through the Helix-Loop-Helix domain. 4. Reporter genes are designed to report upon whether or not what event has happened? (2 points) 5. For each underlined pair of terms, circle the one that is correct. (½ point each) In the paper by Hoare et al., Tnk1/Kos1 is a putative oncogene/tumor suppressor gene which affects the activity of Raf/Ras. To study this gene, Hoare et al. deleted/overexpressed Tnk1 in mice. The Tnk1 protein is a kinase/phosphatase.

4 BIO360 Quiz 4 October In the diagram below from the paper by Hoare et al., why is it necessary to have TK in the targeting construct? 2. In the diagram below, what is represented by the black box that I circled with a dashed line? 3. What is the principle way that the Rb protein is regulated through the cell cycle? A. protein degradation B. acetylation C. phosphorylation D. transcriptional activation E. transcriptional repression 4. To determine if the E2F-1 protein and the DP-1 protein are bound to each other in a living cell, which technique should I use? A. microarray B. methylation-specific PCR C. coip D. sirna E. northern blot 5. A portion of a figure from the Hoare et al. paper is shown on the right. The lane labels refer to Tnk1 genetic status of the cells used in the western blot. In one sentence or less, what is the conclusion of this experiment?

5 BIO360 Quiz 5 October When the E2F-1/DP-1 heterodimer is bound to an enhancer and prb is highly phosphorylated, the transcription of nearby genes is A. Repressed B. Derepressed C. Activated D. Deactivated (1 point) 2. p53 is a tumor suppressor gene that is frequently mutated in human cancers. As discussed in the review by Vogelstein et al. ( Cancer Genome Landscapes ), most mutations in tumor suppressor genes are deletions. Unlike most tumor suppressor genes, why are 95% of the cancer-associated mutations in p53 substitution mutations in the DNA binding domain? (3 points) 3. Classify each of the following proteins as anti-apoptotic, pro-apoptotic, both or neither. (½ point each) Apaf-1 Anti-apoptotic Pro-apoptotic Both Neither ATM Anti-apoptotic Pro-apoptotic Both Neither Bcl-2 Anti-apoptotic Pro-apoptotic Both Neither p53 Anti-apoptotic Pro-apoptotic Both Neither 4. You identify a protein in lab and find that it contains four BH domains (BH1, BH2, BH3 and BH4). Based on this fact, what do you hypothesize the function of this protein will be? (2 points) 5. The paper by Zhang et al. places three molecules into a sequential pathway. Which is the correct order of how these three molecules affect each other? (2 points) A. p53 DYRK1A mir-1246 B. p53 mir-1246 DYRK1A C. DYRK1A mir-1246 p53 D. DYRK1A p53 mir-1246 E. mir-1246 p53 DYRK1A

6 BIO360 Quiz 6 October Name one technique that could be used to answer each of the following questions: (1 point each) Upon the overexpression of the DYRK1A kinase, which human genes become transcriptionally activated? Does the Ets1 transcription factor bind to the DNA near the RB promoter in vivo? Does the deletion of the E2F-2 gene affect the amount of Apaf-1 mrna in a living cell? Do the E2F-4 and DP-2 proteins bind to each other in vivo? What proportion of my cultured cells are in G 0? 2. A portion of Figure 4A from the Zhang et al. paper is shown on the right in which an inhibitor of mir-1246 (or control oligonucleotide) was added to these cells, which were subsequently treated with etoposide or left untreated. Assuming that the model of Zhang et al. is correct, what will these two lanes in these western blots show for the levels of DYRK1A, p53 and Actin? Please briefly explain your answer. (3 points)? 3. Telomere shortening leads to (2 points) A. Cell senescence B. Apoptosis C. Transformation D. Metastasis E. Immortalization

7 BIO360 Quiz 7 November 4 1. Name the two proteins encoded by the INK-ARF locus and briefly describe the function of each. (3 points) 2. The diagram on the right helps to explain cellular senescence. Label both axes and circle the one point on the diagram where most cells enter senescence. (3 points) 3. Imagine that instead of LIN52-Ser28 phosphorylation controlling assembly of the DREAM complex, what actually happens is that phosphorylation of LIN37-SER182 allows the MMB complex to form. In that case, what would Livtochick et al. s coip experiment have looked like? Draw in bands for the missing four lanes on the figure below. (4 points)

8 BIO360 Quiz 8 November 11 2 points each 1. pvhl directly transfers a ubiquitin molecule to HIF1- and thus would be classified as a(n) A. Ubiquitin Ligase. B. Ubiquitin Esterase. C. Ubiquitin Activating Enzyme. D. Ubiquitin Conjugating Enzyme. E. Ubiquitin Lyase. 2. What cell type makes up the wall of capillaries and other blood vessels? 3. Interruption of Integrin binding commonly leads to which phenotype? A. Apoptosis B. Proliferation C. Quiescence D. Senescence E. Genomic instability 4. Tumors frequently become resistant to chemotherapuetic drugs over time. Why are angiogenesis inhibitors expected to avoid this problem? 5. According to Chaffer and Weinberg, what are the two phases of cancer cell metastasis?

9 Fold Enrichment BIO360 Quiz 9 November Alphabet Soup: What does each of the following acronyms stand for? Answer any five of the six. (1 point each) DSB EMT HR MMP NER NHEJ 2. In one sentence or less, what is the question that Fang et al. were asking in the figure shown on the right? (2 points) 3. BRG1, p300 and Sp1 are all proteins that are believed to form a complex on the SPD promoter. Each gene was knocked down using the indicated shrna, followed by IP of one of the three proteins and PCR for the SPD promoter. Based on the data below, draw which protein binds to which other proteins on this promoter. (3 points) Sp1 ChIP p300 ChIP BRG1 ChIP shrna NS Sp1 BRG1 p300

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