Question

When a stem cell undergoes asymmetric cell division, what are the two cell types typically formed?

List three ways stem cells protect their genomic DNA.

What are the two main lineages derived from hematopoietic stem cells? List two differentiated cell types derived from each lineage.

Some people believe that cancers form from mutated stem cells. What data from the study of CML supports this theory?

Many DNA polymerases have two catalytic activities. What are they?

What is the phenotype of a mouse in which the proof-reading activity of DNA polymerase has been eliminated through mutation?

When a mistake occurs during DNA replication, it is important for the cell to identify which base is correct and which is incorrect. What clue is used by the repair machinery to determine which base(s) to remove?

What is a microsatellite and how can they lead to random base insertions and deletions in the DNA sequence?

Some (but not all) cancers display microsatellite instability. How does this instability usually arise?

Many bases undergo deamination, but deamination of 5-methylcytosine is very frequent. What base is formed when 5-methylcytosine undergoes deamination?

What products are formed from single electron reduction of O2 to H2O?

Name 3 sources of reactive oxygen species in living tissue.

Would you expect a mouse with a deleted 8-oxo-deoxyguanosine glycosylase to have a higher or lower cancer risk?

Compare how X rays and UV damage DNA.

What are the two major photoproducts formed by UV radiation?

Many environmental agents can alkylate DNA. What is the specialized repair mechanism used by the cell to repair this type of damage?

Many carcinogens enter the body as non-reactive pro-carcinogens. How do they become carcinogens?

Why do cytochrome P450 enzymes attach oxygen molecules to pro-carcinogens?

List three cytochrome P450 substrates that are thought to be human pro-carcinogens and indicate where they come from.

Many dietary pro-carcinogens are absorbed by the small intestine. What is their next destination and where does most of their metabolism usually occur?

What are phase I and phase II enzymes?

What is glutathione and how do glutathione-S-transferases protect cells from carcinogens?

Name a cruciferous vegetable and one of its “active” ingredients with regard to cancer prevention.

How does sulforaphane impact Keap1 and Nrf2 in the cell? What kind of proteins are Keap1 and Nrf2?

Compare base excision DNA repair and nucleotide excision repair. What types of lesions are repaired by BER and which are repaired by NER?

How many XP genes are there? Are XP individuals homozygous or heterozygous at a mutant XP locus?

Most of the XP genes encode proteins involved in: ____________.

Approximately how many base pairs are replaced following NER and BER?

Are BRCA1 and 2 genes best viewed as gatekeeper or caretaker genes?

There are two ways a cell can repair a double strand DNA break. What are they called and which is more error prone?

Which double strand break repair pathway requires a sister chromatid?

What is the difference between chromosomal instability and microsatellite instability? How do these states arise?

In a normal cell, mitosis will not occur until the spindle assembly checkpoint in passed. What event satisfies the spindle activated checkpoint? What happens when this checkpoint in deficient?

What is the role of centromere tension for passing the spindle assembly checkpoint?

Answer 1

1) When stem cells undergo aymmetric division, it produces two daughter cells- one is the stem cell original copy and the other is the differentiated cell that is not a stem cell

2) Three ways by which the stem cells protect their genomic DNA are:
- By selective segregation of the template DNA
- Altruistic apoptosis of the mutated sequenced cells
- The outer tissue of the stem cell confers the final protection.

3) The two lineages that are derived from the hematopoeitic stem cells are : Myeloid and Lymphoid cells.
Myeloid stem cells can differentiate into many other cells like -eosinophils and erythrocytes. The lymphoid cells differentiate into - natural killer cells and B lymphocytes.

4) Chronic myeloid leukaemia is a type of cancer that is caused by the unregulated growth of the myeloid cells while in the bone marrow. CML is basically the cancer of white blood cells and because these are the differentiated cells from the myeloid progenitor cells, mutations in the precursor cells lead to the development of cancer.

5) The two catalytic mechanisms of some DNA polymerases like Pol beta are :
- Synthesis of DNA nucleotides in replication
- DNA repair mechanism for AP sites by deoxyribose phosphate lyase

6) DNA proofreading activity of the DNA polymerase helps in checking the incorporation of the wrong bases leading to mutation that might lead to cancer or other mutational diseases. The mouse having eliminated proof reading activity has a mutator phenotype where the mutation rate is more than the proofreading rate and may lead to cancer.

7) The DNA polymerase has a cleft like structure that is required to fit the OH region of the correct base pair. If the base pair incorporated is wrong , the alignment of the bases is disturbed and no perfect phosphodiester bonds are formed. The polymerase immediately slides to the proofreading area and removes the wrong base.

8) Microsatellites are certain repetitive DNA motifs that are randomly repeated in the genomes many times. They cause point mutations by inserting wrong bases in the strands of the DNA. Also thet cause mismatch in the DNA strands leading to slippage of the DNA . The error rate of the DNA polymerase for the repetitive microsatellites are much higher thereby allowing easy mutations.

9) The microsatellite instability occurs due to the DNA mismatch repair that has been impaired. Microsatellite insertions causes the repair mechanism to be abnormal leading to poorly differentiated tissues or higher mutational rates or abnormal homologous chromosomal recombinations leading to cancers.

10) When 5-methylcytosine is deaminated, it forms thymine

11) The products formed from single electron reduction are : superoxide anion radical, hydrogen peroxide, hydroxyl radical and water.

12) Three sources of ROS are:
- Mitochondria during the ETC
- Xenobiotics
-  immune cell signaling via the NOX pathway

13) 8-oxo-deoxyguanosine glycosylase is involved in the base excision repair. Mutation of this enzyme will have a higher cancer risk as the repair mechanism would be impaired.

14) X rays causes breakage of the sugar phosphate backbone of the DNA whereas the UV rays causes thymine-thymine dimerization that forms a bulge in the DNA strands.

15) The two major photoproducts formed are :
- Cyclobutane pyrimidine dimers
- (6-4) photoproducts

P.S. Try posting the rest of the questions separately as all cannot be answered according to Honor code.