Cell Cycle II (Sept. 15 - Schultz)

Question 1

List the 6 steps of cell replication

Answer 1

1. prophase
2. metaphase
3. prometaphase
4. anaphase
5. telophase
6. cytokinesis

Question 2

Nuclear membrane is composed of these 2 structural elements…

Answer 2

1. Lamin (not to be confused with laminin)

2. Intermediate filaments

Question 3

How is the nuclear envelope degraded

Answer 3

Lamin is degraded by phosphorylation by M-Cdk. This causes the breakdown during mitosis. Dephosphorylation of the amine reverses this process.

Question 4

What is the structure of centrosomes?

Answer 4

Pair of centrioles surrounded by pericentriolar matrix

Question 5

How are centrioles replicated?

Answer 5

At G1: the centriole pairs separate
At S phase: a progeny centriole begins to grow near the base of the parent centriole at a right angle to the original.
The replication is complete by G2 phase.
At M phase the parent/progeny combo separates together as a pair into the mother and daughter cell.

Question 6

What is an aster and how does it relate to the centrosome?

Answer 6

An ASTER is the radial array of microtubules that originate from the centrioles.
They are part of forming the centrosome gamma tubulin ring complexes and the growing microtubules comprising the MTOC of animal cells

Question 7

In which direction do microtubules (MTs) grow?

Answer 7

Minus to Plus end -towards periphery of cell - away from the centrosome.

Question 8

What is the function of MAPs

Answer 8

microtubule associated proteins stabilize the plus ends and promotes polymerization and growth.
Result: longer, less dynamic microtubules

Question 9

What does catastrophin (kinesin 13) do?

Answer 9

Promote destabilization of MT polymers - result in shorter, more dynamic MTs

Question 10

What are the 3 classes of dynamic microtubules in mitotic spindles of animal cells?

Answer 10

1. Kinetochore MT - attach each chromosome to the spindle pole
2. interpolar microtubules - hold the two halves of the spindle together
3. astral MT - interact with the cell cortex - act like an anchor

Question 11

What is the function and structure of condensin?

Answer 11

• 5 subunit protein complexes (Smc2, Smc 4, Cap-G, Cap-H, Cap-D2
• catalyzes restructuring and compaction of chromosome DNA.
• Hydrolyzes ATP to coil DNA

Question 12

What is the function and structure of cohesion?

Answer 12

• 4 subunit protein complex (Smc1, Smc3, Scc1, Scc3) with ATPase domain at one end
• Form ring structure and may encircle sister chromatids which are compacted around histones

Question 13

What DNA repeat sequence is found at human centromeres?

What is usually flanking these repeats?

Answer 13

A-T repeats

Surrounded by pericentric hterochromatin

Question 14

Describe the DNA organization of the chromatin that forms the centromere of human chromosomes

Answer 14

• H3 histone is substituted for CENP-A histone at kinetochore binding site.
• Chromatin with normal H3 is dimethylated at lysine 4

Question 15

How many proteins are found in the kinetochore?

Answer 15

At least 12

Question 16

What is the function of ATM/ATR? How and when are they activated?

Answer 16

Kinases which activate p53.

Activated through DNA damage before entering M-phase

Question 17

What are Chk1/2 kinases?

Answer 17

Kinases which inactivate the M-Cdc25 phosphatase…prevents Cdc25 from removing inhibitory phosphate on M-Cdk.

Question 18

What happens if DNA damage is extensive and p53 is highly expressed?

Answer 18

mitotic catastrophe (apoptosis)

Question 19

What is the function of the APC

Answer 19

(APC) -anaphase promoting complex - leads to sister-chromatid separation in dividing cells
(Functions as an E3-Ubiquitin Ligase)

Question 20

What is the function of securin?

Answer 20

Holds separase protein in an inactive conformation

Question 21

What does Separase protein do?

Answer 21

When active, separate cleaves associated cohesin complex by cleaving Scc1 subunit. This allows sister chromatids to separate.

Question 22

True or False: CDK inactivation in anaphase promotes separase activation by allowing its dephosphorylation?

Answer 22

TRUE: M phase cyclin degradation inactivates M-Cdk1 complex allowing separase activation because of NO phosphorylation

Question 23

Describe the process of which CDC20 and APC promote sister chromatid separation

Answer 23

An inactive APC by CDC20 binding leads to ubiquination and destruction of securin. Destruction of securin allows separase to become active and cleave cohesins to allow sister chromatids to separate

Question 24

What is the function of M phase cyclins

Answer 24

Activates M-CDK1.

Allows phosphorylation of separase - inhibits sister chromatid separation

Question 25

What happens when kinetochores are all attached to MTs?

Answer 25

CDC 20 is activated and binds to APC complex to promote degradation of securin

Question 26

How many chromatids are present that need to have their kinetochores attached to microtubules?

Answer 26

46 chromosomes -> 92 chromatids need to be attached

Question 27

What is the “wait signal”

Answer 27

Period that ensures all kinetochores are attached to microtubules.
Single inhibitory signal given by unattached kinetochore is sensed and deciphered

Question 28

What are the proteins that would override anaphase wait and create an “abnormal go” signal that leads to forced cell division?

Answer 28

Increase in:
-Aurora kinases
-Survivin
-CDC20
Decrease in:
-BubR2 kinase

Question 29

What will happen to a cell that is left in the “no go” stage or is left paused for a long time?

Answer 29

Taxol promoted (apoptosis inducing drug)
Mitotic catastrophe & apoptosis

Question 30

What is the function of the Mad2 complex?

Answer 30

Mad2 binds to unattached kinetochores and sequesters/inactivates CDC20.
This prevents the CDC20 from binding to APC and causing progression of cell cycle

Question 31

What will happen with an “abnormal go” signal?

Answer 31

• Polyploidy

- Genetic instability