1. What are the major types of DNA damage repaired by each of the following pathways: (a) photoreversal, (b) base excision repair, (c) nucleotide excision repair, and (d) mismatch repair?.
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2. Specify which of the repair pathways (a, b, c, and/or d) listed in the previous question is associated with each of the following enzymes, protein complexes or gene products: CSB, AP endonuclease, hMSH2, DNA photolyase, ERCC6, MutH, XPA, uracil DNA glycosylase, DNA ligase, RAD3, TFIIH, DNA polymerase.
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1. Name 2 human diseases caused by defects in different DNA repair pathways (that is, one of the 2 diseases you name should be in one repair pathway and the other disease should be in a different pathway). List (briefly!) the steps in each pathway and then, in more detail, describe the normal function in that pathway of the protein encoded by the gene, which, when mutated, can cause disease.
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Click here for answers to questions 1, 2 and 3 from April, 1998.
1. Draw a structural diagram of the compound resulting from deamination of 5-methyl cytosine. (7 points)
2. What is the name of this compound? (1 point)
3. Which of the following repair pathways are capable of repairing the damage resulting from deamination of 5-methyl cytosine: (4 points)
Click here for answers to questions 1, 2 and 3 from November, 1998.
4. List the mammalian proteins known to be required for double-strand break repair by non-homologous end joining. Using no more than 10 words per protein (hopefully only one or two words), describe what is known about the function of each of these proteins. (8 points)
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5. In no more than one sentence, describe what is meant by "transcription-coupled repair." (5 points)
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1. Draw a structural diagram of the oligodeoxynucleotide 5'-dC-dG-dT-3', both before and after loss of the G due to spontaneous depurination. Show the sugar-phosphate backbone, but don't worry if you can't remember the positions of the amino and keto groups in the C, G and T bases. Indicate the positions of those groups if you can, but otherwise simply show the skeleton of the pyrimidine or purine base, as appropriate. (7 points)
2. What is the name of the site in the oligodeoxynucleotide of question 1 from which the G has been lost? (1 point)
Click here for answers to questions 1 and 2 from November, 1999.
3. Are any of the following repair pathways capable of repairing the damage resulting from loss of G by depurination? If so, which one(s)? Direct reversal by photolyase? Direct reversal by O6-methylguanine-DNA methyltransferase? Mismatch repair? Base excision repair? Nucleotide excision repair? Double-strand break repair by homologous recombination? Double-strand break repair by non-homologous end joining? (4 points)
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4. List the bacterial proteins known to be required for nucleotide excision repair. Using no more than 10 words per protein (hopefully only one or two words), describe what is known about the function of each of these proteins. (4 points)
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5. If T is in one strand of a DNA molecule and G is in the complementary strand, is there a problem? If you think that this situation may represent a problem (or potential problem) for a cell, then in no more than two sentences explain why it might be a problem. (4 points)
6. List all of the repair pathways you can think of that are capable
of repairing a situation where T is in one strand and G is in the complementary
strand. For each pathway that you list, use a few words (no more than one
sentence) to explain why you think this pathway is capable of repairing
this situation. (4 points)
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1. Draw a diagram of the DNA base, adenine. Show the positions of any keto, hydroxyl or amino groups. You may number the ring system if you wish, but it is not necessary. (5 points)
2. On the diagram you have just drawn, circle the positions that can be methylated by S-adenosyl methionine. Which position is most readily methylated? (2 points)
3. Which of the following pathways is responsible for correcting adenine methylation: (a) photolyase; (b) mismatch repair; (c)base excision repair; (d) nucleotide excision repair; (e) transcription-coupled repair, (f) non-homologous end joining? (2 points)
Click here for answers to questions 1, 2 and 3 from October, 2000.
4. Using no more than four sentences, describe how bacteria and mammalian cells distinguish the template strand from the nascent strand during mismatch repair. (5 points)
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5. Which proteins DIFFER between the global genome repair (GGR) and transcription-coupled repair (TCR) pathways? Briefly describe the presumed role of each of these different proteins (in GGR or TCR). Do NOT describe the roles of proteins used in common by GGR and TCR. 5( points)
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6. Briefly describe why people suffering from the disease "Xeroderma pigmentosum variant" are sensitive to sunlight. (5 points)
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1. (5 points) Draw a diagram of a cyclobutyl pyrimidine dimer (CPD). There's no need to draw the sugar and phosphate groups in detail; just call them "sugar" and "phosphate" or other abbreviation. Do show the pyrimidine ring structure in sufficient detail to make clear which ring constituents are nitrogens and which are carbons, and do show the cyclobutane ring connected to the correct positions on the pyrimidine rings.
2. (2 points) Which DNA bases can form CPDs? Which bases are found in the most common type of CPD?
3. (2 points) Which of the following pathways is/are responsible for repairing CPDs? (a) photolyase; (b) mismatch repair; (c)base excision repair; (d) nucleotide excision repair; (e) homology-based double-strand break repair; (f) non-homologous end joining; (g) damage bypass
Click here for answers to questions 1,2 and 3 from November, 2001.
4. (5 points) Using no more than four sentences, explain why the vast majority of HNPCC patients have defects in the MSH2 or MLH1 genes rather than in MSH3, MSH6, PML2 or MLH3.
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5. (5 points) Both non-homologous end joining (NHEJ) and single-strand annealing (SSA) lead to imperfect joining of DNA ends. What striking structural difference would you expect to find between ends joined by NHEJ and ends joined by SSA?
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6. (6 points) Very briefly describe two pathways of DNA damage bypass, one error-free and one error-prone.
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1. (4 points) In a few words, please list the types of DNA damage that are repaired by each of the major excision repair pathways: (a) mismatch repair (MMR), (b) base excision repair (BER), (c) nucleotide excision repair (NER).
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2. (6 points) Which specific repair pathway(s) is/are primarily responsible for repairing the following types of damage? In answering this question, you should consider non-excision pathways such as homologous recombination in addition to excision pathways such as BER.
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3. (5 points) Please draw a simple diagram to illustrate the differences between repair by synthesis-dependent strand annealing and repair by single-strand annealing. Use no more than a few words where necessary to explain your diagram.
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4. (5 points) Using a few words and/or a simple diagram, explain how the Rad50 protein may facilitate the holding together of broken DNA molecules.
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5. (5 points) Provide a plausible explanation for the biological importance of DNA damage bypass. How is cell survival enhanced by permitting replication forks to continue through sites of unrepaired DNA damage? Please answer using no more than four sentences.
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1. State one reason why the process of DNA repair is important. Use no more than two sentences (3 points).
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2. List the names of the three types of excision repair. Provide only the names; do not describe the processes (3 points).
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3. List the steps of nucleotide excision repair (NER) that are common to bacteria and eukaryotic organisms. Do not list any steps that are specific to bacteria or eukaryotes, and do not use specific protein/enzyme names. I'm looking for a simple description of the basic steps of NER (6 points).
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4. In one sentence, please describe the role of the Artemis protein in non-homologous end joining (4 points).
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5. Which protein is the target of the ubiquitination events that take place during DNA damage bypass (3 points)?
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6a. In the absence of external mutagens (no chemicals, no radiation), what is the most common type of DNA damage (3 points)?
6b. What DNA repair pathway(s) are used to repair that damage (3 points)?
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1. Why do nearly all cases of hereditary non-polyposis colon cancer (HNPCC) involve mutations in MSH2 or MLH1? (Please use no more than three sentences in your answer)
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2. Which proteins function specifically in transcription-coupled nucleotide excision repair (TC-NER)? Please do not list proteins that have roles in both global genome repair (GGR) and TC-NER. (Please simply list the proteins; do not explain their roles).
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3. Please describe the basic steps of double-strand break repair by nonhomologous end joining (NHEJ). I encourage you to use simple diagrams to assist with your explanations, but diagrams are not necessary.
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4. (a) Which repair processes use polynucleotide kinase (PNK)? (simple list)
(b) What are the roles of PNK in these repair processes? (two sentences or less)
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5. In order to promote damage bypass by recombination, should PCNA be mono-ubiquitinated or poly-ubiquitinated? (one-word answer)
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Question 1:
a) Please draw the structure of the nucleic acid base, cytosine. Just show the structure. It is not necessary to show the numbering (4 points).
b) Please draw the structure of the base that results from deamination of cytosine (4 points).
c) What is the name of the base that results from deamination of cytosine (1 point)?
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Question 2:
Which of the following DNA repair pathway(s) are able to repair DNA molecules containing deaminated cytosines? If you're uncertain, explain why you're uncertain (3 points).
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Question 3:
For each of the repair pathways listed below, please state whether, to accomplish gap filling, the pathway employs standard DNA replication enzymes (polymerase δ or ε; PCNA; DNA ligase I), or alternative DNA synthesis enzymes (β-family polymerases; XRCC1 or XRCC4; DNA ligase III or IV), or both (3 points)?
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Question 4:
Please name a disease that is caused by a mutation in a gene that affects DNA repair. For the disease that you named, list the gene or genes in which mutations can cause the disease. For any one of the genes in your list, explain (in no more than two sentences) the function in DNA repair of the protein encoded by the gene (5 points).
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Question 5:
Imagine that you've discovered a new gene called YFG that contributes to DNA repair efficiency. You notice that cells carrying YFG mutations frequently stop dividing and become senescent. Do you think that mutations in the YFG gene are likely to cause cancer? In no more than two sentences, please explain why you think YFG mutations might, or might not, lead to cancer (5 points).
Click here for answer to question 5 from November, 2005.
1. (5 points) Which specific repair pathway(s) is/are primarily responsible for repairing the following types of damage? In answering this question, you should consider non-excision pathways such as homologous recombination in addition to excision pathways such as BER.
Click here for answer to question 1 from November, 2006.
2. (10 points) Describe two cases in which protein ubiquitylation contributes to DNA repair. In each case, name the protein(s) that serve as ubiquitin-conjugating enzymes or ubiquitin ligases, and name the protein(s) that are ubiquitylated. In each case, briefly describe the importance of the ubiquitylation for successful repair.
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3a. (2 points) With which protein(s) does human MutSα-MutLα interact in order to distinguish the newly synthesized strand from the template strand at a mismatch?
3b. (3 points) List the final steps of mismatch repair in human cells, after MutSα-MutLα has identified the newly synthesized strand.
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4. (5 points) Using one sentence or less in each case, describe a function for each of the following during double-strand break repair:
Click here for answer to question 4 from November, 2006.