Cell Cycle I (Sept. 15 - Schultz)

Question 1

In steady state conditions, approximately how many cells are generated and recycled to maintain homeostasis?

Answer 1

1 million cells…10^6 per second

Question 2

Describe the cell cycle beginning with the 1 st step of interphase

Answer 2

G1 -> S phase -> G2 -> M phase

Question 3

What are the similarities and difference between senescence and quiescence?

Answer 3

In both senescence and quiescence, cell has entered G0 phase.

However, senescence is the permanent entry of the cell into G0 (adult brain cell). While in quiescence, the stationary G0 phase can be overcome by addition of growth factors and re-synthesis of CDKs

Question 4

Which cell cycle phase is described as the commitment phase?

Answer 4

S-phase -> once cell has committed to replication it will enter S-phase and will proceed all the way through the cell cycle

Question 5

What is the G1 checkpoint

Answer 5

Decision of the cell to enter S phase.

Is environment favorable?

Question 6

What is the G2 checkpoint

Answer 6

Decision of the cell to enter M phase.
Is all DNA replicated?
Is environment favorable?

Question 7

What is the metaphase checkpoint?

Answer 7

Decision whether to exit M phase (specifically metaphase)

Are all chromosomes attached to the spindle?

Question 8

What is meant by “favorable environment”?

Answer 8

Presence of specific growth factors to allow cell replication

Question 9

What are the two key components of the cell-cycle control system?

Answer 9

Cyclin forms a complex with cdk (cyclin-dependent kinase) -activates to trigger a specific event. W/o cyclin, Cdk is inactive

Question 10

True or False: CDKs are degraded when not being used

Answer 10

False: CDKs are constitutively present. However, they are only activated through cyclin and their proper phosphorylation

Question 11

Describe the regulation of Cdk by phosphorylation in tandem with the binding of cyclin

Answer 11

Wee1 kinase adds inhibitory phosphates in addition to activating phosphates added by CDK-activating kinase (CAK).

Question 12

How is inactive Cdk activated after cyclin has been bound and inhibitory phosphate is added?

Answer 12

CDC25 phosphatase cleaves inhibitory phosphates and allow CDK to become active.

Question 13

List the 2 simplified sets of machinery used in regulation of the cell cycle…(these include the cyclins, CDKs…think cell cycles

Answer 13

1. • G1/S-cyclins & associated CDKs
     - G1/S CAKs/CDC25 and Wee1
     - SCF (E3 ubiquitin ligase protein complex)
2. -M cyclins & associated CDKs
   - M CAKs/CDC25 and Wee1
   - APC (anaphase promoting complex)

Question 14

What is the role of Rb protein in the cell cycle regulation?

Answer 14

Active Rb protein (not phosphorylated) sequesters E2F - which is a transcription factor protein which promotes S-phase gene transcription.
Phosphorylation of the Rb protein causes its inactivation releasing E2F -> up regulating gene transcription.

Question 15

What does the E2F protein act upon and what are its effects in the cell cycle?

Answer 15

E2F creates more G1/S-cyclin (cyclin E) + S-cyclin (cyclin A) -> activates S-CDK and causes entry into S-[hase (DNA synthesis)

Question 16

Describe the effect of certain viral proteins acting as competitive inhibitors to Rb binding pocket

Answer 16

Epstein Barr Virus is an example of a oncogenic viral protein which displaces E2F and causes cell to avoid checkpoint regulation -> causes unintentional up regulation and cell proliferation

Question 17

How does p53 regulate the cell cycle and fulfill its role as the “superhero - guardian of the cell cycle?”

Answer 17

DNA damage causes arrest of the cell cycle in G1 through phosphorylation of p53. The activation of p53 causes dissociation of Mdm2 and allows p53 to accumulate in the cell. High levels of p53 cause p21 CKI protein to be expressed. This p21 binds and inactivates to G1/S complexes

Question 18

What protein usually causes p53 to be degraded by proteasomes? Why does this protein exists?

Answer 18

MDM2.

This protein normally sequesters the constitutively expressed p53 and promotes its ubiqutination and destruction

Question 19

How does p21 inactivate G1/S complexes

Answer 19

p21 CKI binds to both G1/S cyclin and CDK and inhibits the entire complex

Question 20

High levels of DNA damage can lead to a very high level of p53. This can cause…?

Answer 20

Apoptosis

Question 21

What is the point of having the cell arrest in G1 stage if it encounters DNA damage?

Answer 21

Allows cell/ gives the damaged cell time to fix the damage before continuing replication