DNA Repair Exam Questions by mur41479


									DNA Repair Exam Questions:

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?.

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.

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.

General Cancer Questions

List and define 4 stages of chemical carcinogenesis. (2 points)

Influenza virus, a virus with an RNA genome, does not transform cells because: (3 points)
 a. it's defective in replication
 b. it's genome contains onc sequences
 c. it integrates into the wrong part of the genome
 d. it's life cycle contains a reverse transcription step and the DNA integrates adjacent to
the c-myc proto- oncogene
 e. it's life cycle contains no DNA molecule which can be stably maintained within the cell
 f. all of the above
 g. none of the above

18. Adenoviruses and Papovaviruses: (3 points)
 a. transform permissive cells
 b. attack proteins of the G1/S checkpoint
 c. have early and late genes
 d. express only late genes when transforming cells
 e. inhibit apoptosis through interactions with p53
f. stimulate terminal differentiation through transcriptional activation of the RB gene
g. answers b, c, and e
h. answers a, b, and e
i. all of the above
j. none of the above

19. Epstein-Barr Virus: (3 points)
 a. is a Herpes virus
 b. is associated with Burkitt's lymphoma
 c. is associated with nasopharyngeal carcinoma in Southern China
 d. infects almost everyone
 e. usually remains latent for an infected person's lifetime
 f. some of the above, but I'm not sure which
 g. all of the above
 h. none of the above

What is the difference between a oncogene and a proto-oncogene? (2 points)

21. What type of experiment first implicated tumor suppressor genes in cancer? (2 points)

22. The p53 gene is a ____ _____ gene. (2 points)

23. If you mutagenized the Rous Sarcoma Virus so that it would grow at and produce foci at
35oC and not produce foci but
would grow at 41oC, then what theory would you support? (2 points)

24. In mice that lack both alleles of the p53 gene (the p53 "knockout" mouse),what
phenotype do they display?
 (2 points)

25. The first experiment to indicate that human tumors might harbor altered genes and
that these altered genes might
contribute the the malignant phenotypewas an experiment where DNA from _______ ____
was transfected into NIH3T3
cells and _______ ____ formation was observed. (2 points)

26. The "2-hit" hypothesis of Knudson concerns the number of ___ ________required for
sporadic retinoblastoma to occur.
(2 points)

27. Varmus and Bishop won the Nobel Prize in Physiology and Medicine in 1989 for an
experiment that indicated that RNA
tumor viruses have a specific gene that transforms cells from the normal state to the
malignant state (i.e., they contain an
oncogene within their genome). Briefly describe this experiment and
the reasoning behind it . (10 points)
28. Ras was the first human oncogene to be isolated. (14 points)
 a. What is its normal function?
 b. What cellular pathway(s) does ras function in?
 c. How is it altered in cancer?
 d. What change in function occurs when ras is mutated in human cancers?
 e. How does this altered ras activity disrupt the normal signal transduction pathway that
ras functions in?

protein machines operate through a series of ordered
conformational changes in the various constituent proteins. For the RAS signal transduction
pathway, give one example of a
conformational change in a protein that allows it to interact with another protein. Name
both proteins - the one under-going
the conformational change and the one with which it then interacts. (3 points)

Which cytoskeletal component is responsible for the assembly and location of the
endoplasmic reticulum and Golgi
apparatus? Which cytoskeletal component is closely linked to cell development and
 (3 points)

Indicate which type of mutations (i.e., null mutation, over-expression, loss or gain of binding
specificity, etc.) could be
oncogenic if affecting each of the following: (10 points)

a. Rb

b. p16

c. cyclin D

d. Cdk4

You are studying a new small DNA tumor virus, HP. You have set up an in vitro DNA
replication system based on what
is known about SV40 DNA replication. You have found that you can reconstitute leading and
lagging strand synthesis on a
plasmid containing the viral origin of replication using the following proteins: viral protein E
(which you know binds to the
viral origin of DNA replication), replication protein A (also known as RPA or RFA), PCNA,
RFC, topoisomerases I and II,
DNA polymerase alpha-primase, DNA polymerase delta, and DNA polymerase epsilon. You
then carry out replication
reactions in the absence of each of the individual proteins. You note two differences
between what is known about SV40
DNA replication and what you see with HP DNA replication. First, in the absence of DNA
polymerase delta, you detect
only long products on denaturing gels. Also, in the absence of DNA polymerase epsilon, you
do not detect long products, or
the short products (300 to 600 nucleotides) characteristic of Okazaki fragments, but you
do detect a very small level of
synthesis of DNA chains of about 30 nucleotides. Based on this information and what you
know about SV40 DNA
replication, give me a hypothesis of what you believe the roles of DNA polymerases delta
and epsilon are in HP viral DNA
replication. Also propose an experiment that could provide additional evidence of your
hypothesis. Be brief! (12.5 points)
As scientists in oncology, it is important to recognize persons who exhibit characteristics
consistent with inherited
susceptibility to cancer. List three (3). (3 points)

6. With regard to genetic screening and testing, which of the following statements are
true? (2 points)
 a. Genetic screening is recommended for all women of Ashkenazi Jewish background since
mutations in BRCA & BRCA2
occur more frequently in this population.
 b. There is Federal legislation in place that specifies that an individual cannot be
discriminated against, with regard to
health insurance, based on their genetic status.
 c. Scientists, who through their cancer genetics research, learn that an individual has a
genetic mutation in the gene
ultimately identified, are obligated (directly of through the physician) to offer the
individual the information of that finding
for clinical purposes.
 d. New York State has specific certification and permit requirements for genetics
laboratories providing clinical testing.
 e. Methods of genetic testing influence the likelihood of detecting an existing mutation.

1. all of the above
2. a, b, c, d
3. a, c, d, e
4. b, c, d, e
5. b, d, e

7. Based on the evolving knowledge and developments concerning genetics and its impact on
health care and research,
scientists and physicians must: (2 points)
 a. keep abreast of advancements in knowledge and technology
 b. effect informed consent of study participants/patients, except for those who are
mentally incapable
 c. address issues surrounding privacy and confidentiality
d. assist in informing and educating participants/patients
e. utilize protocols for all genetics research and clinical studies

1. all of the above
2. a, b, c, d
3. a, c, d, e
4. q, c, d
5. a, b, c

8. Which of the following genetic mechanisms account for development of cancer, either as
currently known or potentially
based on features of these mechanisms? (2 points)
 a. uniparental disomy
 b. chromosomal fragile sites
 c. methylation
 d. expanded nucleotide repeats
 e. altered DNA repair

1. all of the above
2. a, b, c, e
3. b, c, d, e
4. b, c, e
5. c, e

9. Which of the following statements are correct? (2 points)
 a. Chromosomal disorders are generally associated with birth defects and mental
 b. Genetic disorders (Mendelian single gene/pair of genes) are frequently characterized by
effects on biochemical or
metabolic processes.
 c. Autosomal dominant genetic disorders may demonstrate varying extents of physical
manifestations (phenotype), whereas
autosomal recessive disorders pose a more consistent phenotype from family to family.
 d. X-linked recessive genetic disorders affect only males; females are the carriers.
 e. Cancer has been demonstrated in association with chromosomal abnormalities, autosomal
dominant and autosomal
recessive genes, and/or environmental factors.

1. all of the above
2. a, b, c, e
3. a, b, d, e
4. b, c, d, e
5. a, d, e

10. Knowledge of an underlying genetic feature in a participant/patient is relevant to the
scientist or physician because: (2
 a. It may be associated with pathology that impacts participation in a study or influences
medical management.
 b. It may be an indicator of an underlying genetic syndrome or disorder.
 c. It may be segregating in a family, either with or without cancer.
 d. It may be associated with a risk for medical problems other than the presenting feature.
 e. It may influence an analysis/test result.

1. all of the above
2. a, b, c, d
3. a, c, d, e
4. b, c, d, e
5. b, d, e

Describe with examples: (7 points)
a. the genetic map
b. the cytogenetic map
c. the physical map

12. What do the three maps: (7 points)
 a. have in common?
 b. how do they differ?
When a senescent cell is fused to a cell that has the capacity to proliferate, can the hybrid
cell continue to proliferate, can
the hybrid cell continue to proliferate or does it senesce? Why? (3 points)

16. Briefly (three sentences of less!) describe the role of telomeres and telomerase in the
"molecular clock" model for
cellular senescence and how it relates to cancer (I won't be looking for lots of details in
your answer, just the barebones
concept). (3 points)

17. Define the following terms (one sentence or less) (4 points)
 a. mortality stage 1 ("M1")
 b. mortality stage 2 ("M2")

18. Briefly (one sentence or less) describe two lines of evidence which suggest cellular
senescence is related to organismal
aging. (4 points)

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