Lecture 29 - Cell Cycle II

Question 1

What is condensin and what is its function?

L29 S8-9

Answer 1

• 5 subunit protein that forms a ring-like structure
• acts to condense DNA and resolve sister chromatids
• uses ATP

Question 2

What is the mitotic spindle?
What stimulates its formation and what types of microtubules are involved in it?

L29 S10;14-16

Answer 2

• array of microtubules originating from centrosomes on either side of the cell and is used to separate sister chromatids
• formation stimulated by M-cyclin-Cdk complex

Microtubules:

• kinetochore: attaches to chromosomes at the kinetochore
• interpolar: connect microtubules of each pole
• astral: connect pole to cell cortex

Question 3

What are the types of motor proteins used by the mitotic spindle and what function do each serve?

L29 S27-33

Answer 3

Kinesin 5:

• two motor domains that interact with the plus ends of antiparrallel microtubules
• pushes the spindle poles apart by walking toward the plus end of each microtubule

Kinesin 14:

• single minus oriented motor domain connecting antiparallel microtubules
• pulls poles together

Kinesin 4,10:
-plus directed motor domain which pushes chromosomes away from pole

Dynein:
-minus end directed motor pulls astral microtubules towards cell cortex, separating the poles

Question 4

What are the forces responsible for chromosomal movement?

L29 S40-42

Answer 4

Depolymerization:
-depolymerization of the plus ends of kinetochore microtubules pulling the kinetochore to the poles

Microtubule flex:

• microtubules are pulled towards the spindle poles by disassembly at the minus end
• interpolar microtubules also assemble at the positive end

Polar ejection force:

• kinesin 4,10 interacts with chromosome ends pushing them away from the poles
• results in push-pull phenomenon

Question 5

What groups of extracellular signaling molecules regulate cell size and number?

L29 S47-48

Answer 5

Mitogens:
-stimulate cell division by triggering G1/S-Cdk activity

Growth factors:
-stimulate cell growth

Survival factors:
-suppress programmed cell death (apoptosis)

Question 6

Describe cell-cycle entry into S-phase.

L29 S49-55

Answer 6

• mitogen binds receptor
• receptor activates Ras which activates MAP (mitogen activated protein) cascade
• increase of gene regulatory proteins, ie. Myc
• Myc increases expression of G1 cyclins
• G1-Cdk-Cyclin activates E2F proteins
• E2F promotes G1/S cyclin and S cyclin
• cell enters S phase

Question 7

How do Rb proteins regulate the cell cycle?
What disease occurs with improperly functioning Rb proteins?

L29 S56-60

Answer 7

Function:

• Rb protein inhibits E2F protein (promotor of S cyclins)
• entrance into S phase is blocked
• active G1-Cdk phosphorylates Rb protein inhibiting its function

Loss of function of Rb protein results in cancer such as retinoblastoma

Question 8

How do ATM protein kinases effect the cell cycle?
What disease occurs with improperly functioning ATM proteins?

L29 S61-64

Answer 8

Function:

• ATM proteins are activated in response to DNA damage
• ATM proteins phosphorylate Chk1 and Chk2 (checkpoint kinases)
• Chk1/2 targets p53
• p53 targets p21 (CKI)
• p21 inhibits activity of G1/S-Cdk
• progression through cell cycle is blocked

Loss of function of ATM proteins means DNA will not be repaired when damaged. The cell cycle will not know DNA is damaged and will replicate. This is ataxia telangiectasia.