Essay Questions Test Three

Question 1

Describe 3 checkpoints in the cell cycle.

Answer 1

1. Start: cell commmits to cell cycle entry and chromosome duplication (aka restriction point). Cell determines if the environment is favorable to proceed into S phase.
2. G2/M: Chromosome alignment on spindle in metaphase. Cell determines if all DNA is replicated and environement is good to enter Mitosis.
3. Metaphase to anaphase transition: Triggers sister chromatid separation and cytokinesis. Cell determines if all chromosomes are attached to the spindle.

Question 2

What are 2 ways to regulate cyclin Cdk complexes?

Answer 2

1. Inhibition by Wee1 Kinase: this phosphorylates the roof site of Cdk and prevents activation of Cdk by Cyclin. (Cdc25 reverses this)
2. Inhibition by CKI: binds both Cdk and cyclin. Used for control of G1/S cdks and S Cdks in early cell cycle.
3. Proteolysis of S-Cdk’s can remove CKI’s and activate S-Cdk’s

Question 3

Describe the order of events involving APC/C,Cdc20, securin, separase, and cohesin in sister chromatid separation.

Answer 3

APC is activated by the binding of Cdc20. APC/C once acrivated ubiquinates a protein called securin, which inhibits another protein called separase. Securin is protecting cohesin, the protien responsible for holding sister chromatids together along their lengths. Once Securin, a protease, is destroyed separase becomes active and cleaves (separates) the cohesin molecules allowing the sister chromatids to be pulled apart during anaphase.

Question 4

Describe some of the cellular characteristics of Apoptosis.

Answer 4

• Overall shrinkage in volume of cell and nucleus
• Loss of adhesion to adjacent cells
• Formation of blebs on suface
• DNA fragmentation
• Collapse of cytoskeleton
• Nuclear envelope dissassembles
• Engulfment of dying cell by phagocytosis

Question 5

Describe the role of Bcl2 in apoptosis.

Answer 5

Bcl2 regulates intrinsic pathway by regulating the release of cytochrome c into the cytosol by BH123. 4BH domains to block cytochorme c

1. Anti-apoptotic which blocks the release of cytochrome C

Question 6

Describe the role of caspases in apoptosis.

Answer 6

Activation of caspases is a key event in apoptosis.

Cleave target proteins at an aspartic acid residue

Question 7

Describe the role of BH123 in apoptosis.

Answer 7

BH123 is a family of Bcl2 proteins but it is pro apoptotic unlike Bcl2. This group of protiens clusters together to release cytochrome c into the cytosol from the mitochondria outer membrane.

Question 8

Describe the role of BH3-Only protein.

Answer 8

Pro apoptotic protein found in the cytosol, it inhibits Bcl2 protein from inhibiting BH123. This protein translocates to the mitochondria after apoptotic signal activates it. Would be classified as a tumor suppressor gene.

Question 9

Describe the two major forms of caspases.

Answer 9

1. Initiator caspase: induces apoptosis (caspaces 8 and 9)
2. Executioner caspases: destroys actual targets and executes apoptosis (caspase 3). It cleaves downstream proteins and inactive endonucleases, breaks down cytoskeleton and attacks cell adhesion proteins causing the cell to roll up into a ball.

Question 10

What is the role of kinesin-5, kinesin 14, kinesin-4,10, and dynein in chromosome movement?

Answer 10

Kinesin-5 has two motor domains that interact with the plus ends of antiparallel microtubules to push the centrosomes apart.

Kinesin 14 has a single motor domain which walks towards the minus end pulling poles together. Kinesin 5 and 14 work opposite each other to keep the spindle from collapsing.

Kinesin 4,10 is a plus directed motor that pushes the chromosomes away from the pole.

Dynein is a negative end directed motor which pulls the spindles away from each other by linking to the plus ends of astral mictorubules to actin skeleton at the cell cortex.

Question 11

How are oncogenes activated?

Answer 11

Oncogenes can be activated by a deletion or point mutation within the coding sequence creating hyperactive protien in normal amounts. They can also be activated through regulatory mutations upstream crertaing normal protein highly over produced. Activation can also occur through gene amplification in which a normal protein is gretaly over produced. The final way for oncogene activation is through chromosome rearrangements creating normal protein greatly over produced and hyperactive fusiuon proteins.

Question 12

Describe the three forces driving chromosmoe movement in cell division.

Answer 12

1. Depolymerization: The depolymerization of the plus end drives the pulling of the kinetochore forward towards the pole.
2. Microtubule Flux: As depolymerization occurs and the spindles are moved to the spindle poles tubulin is being added at the plus end at the same time so treadmilling is occuring.
3. Polar ejection force: Kinesin-4,10 interact with microtubules and transport chromosomes from the poles resulting in a push and pull motion.

Question 13

Describe ataxia telangiectasia and the lack of ATM kinases in this disease.

Answer 13

A diesease characterized by radiation sensitivity and increased likelihood of cancers due to ATM protien being defective. This protein helps with DNA repair and when it is defective or lacking DNA repair does not occur and mutations build up, it is a recessive mutation. ATM stimulates Chk1 and Chk2 which activate p53 to hault the cell cycle. Without ATM cell cycle arrest never occurs.Some of the characteristic signs of AT are Ataxia, jerky uncoordinated movements, and telangiectatic blood vessels as well as progressive neurological deterioration with exposure to radiation such as X-rays.

Question 14

How does lack of Rb protein lead to retinoblastoma?

Answer 14

Rb is a tumor suppressor protein which prevents over proliferation of cells by regulating the cell cycle. In order to get Retinoblastoma a loss of both copies of Rb must occur. This disease can occur sporadically in which only one eye is impacted, or it can be inherited in which both eyes are affected. The sporadic form is more common. In the hereditary form of Rb a loss of function is inherited in one copy and then a somatic event occurs ridding the cells of the one good copy of Rb leading to LOH and tumors. In the sporadic version all cells are normal and two mutations must occur to both copies of the gene in the same cell.

• Mitogens activate the MAP kinase cascade resulting in E2F activation. E2F binds to the promoters of S-cyclin to promote transcription, leading the cell cycle to occur. Rb is an inhibitor of E2F and if Rb is lacking entry into the S phase has no control and cell division occurs continuously leading to retinoblastoma.

Question 15

What is the difference between a benign and malignant tumor?

Answer 15

A bengin tumor is a non cancerous tumor contained to one area. A malignant tumor is one which breaks through barriers and metastasizes to other areas in the body to begin proliferation at.

Question 16

Why is colon cancer one of the most treatable cancers?

Answer 16

This disease has a very slow progression of ten years, and can be cured before cancer even occurs with screening. A colonoscopy can detect polyps in the colon which is a precursor to colorectal cancer and remove them.

Question 17

How does Gleevec work?

Question 18

Describe heteroplasmy as it relates to mitochondrial genetic diseases.

Answer 18

Heteroplasmy is a mixture of normal mitochondrial cells and mutant mitochondria contained within one cell. There is a certain threshold for mutant mitochondria before disease occurs. The severity of disease depends on the amount of heteroplasmy.

Question 19

Describe the rules of maternal inheritance as it relates to mitochondrial genetics?

Answer 19

Mitochondrial genes are found only in eggs, not sperm, so a mother is the only one who can pass down mitochondria to offspring. If the mother has a defect in her mitochondria it will be passed down to her children, if a father has the defect and not the mother it will end with him.

Question 20

Describe the threshold concept and its relationship to mitochondria genetics disease.

Answer 20

In mitochondrial gene defects a certain number of mutant mitochondria need to be present before disease manifests. There are many mitochondria in cells and one defect out of 100 isn’t enough to cause disease. However, 95 defective mitochondria out of 100 is enough to cause disease. Depending on the type of cell the mitochondria are found in, once the ratio of heteroplasmic mitochondria is tilted towards mutated side disease will occur.

Question 21

Name three properties of cancer cells?

Answer 21

1. Less prone to undergo apoptosis
2. More self sufficient than normal cells
3. Don’t undergo replicative sensense essentially they are immortal

Question 22

Difference between oncogenes and tumor suppressor genes?

Answer 22

Oncogenes are mitogen activating genes that act as cell cycle promoters, similar to a gas pedal. Cancers due to oncogenes occur when there is a gain of function mutation acting like a dominant mutation causing gene proliferation. Tumor suppressor genes are a loss of function mutation which acts recessive, meaning two mutations need to occur for there to be disease. These genes inhibit growth and when they are inefficient nothing regulates the cell cycle and continuous growth occurs.