Cell Cycle I (Sept. 15 - Schultz) Flashcards
In steady state conditions, approximately how many cells are generated and recycled to maintain homeostasis?
1 million cells…10^6 per second
Describe the cell cycle beginning with the 1 st step of interphase
G1 -> S phase -> G2 -> M phase
What are the similarities and difference between senescence and quiescence?
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
Which cell cycle phase is described as the commitment phase?
S-phase -> once cell has committed to replication it will enter S-phase and will proceed all the way through the cell cycle
What is the G1 checkpoint
Decision of the cell to enter S phase.
Is environment favorable?
What is the G2 checkpoint
Decision of the cell to enter M phase.
Is all DNA replicated?
Is environment favorable?
What is the metaphase checkpoint?
Decision whether to exit M phase (specifically metaphase)
Are all chromosomes attached to the spindle?
What is meant by “favorable environment”?
Presence of specific growth factors to allow cell replication
What are the two key components of the cell-cycle control system?
Cyclin forms a complex with cdk (cyclin-dependent kinase) -activates to trigger a specific event. W/o cyclin, Cdk is inactive
True or False: CDKs are degraded when not being used
False: CDKs are constitutively present. However, they are only activated through cyclin and their proper phosphorylation
Describe the regulation of Cdk by phosphorylation in tandem with the binding of cyclin
Wee1 kinase adds inhibitory phosphates in addition to activating phosphates added by CDK-activating kinase (CAK).
How is inactive Cdk activated after cyclin has been bound and inhibitory phosphate is added?
CDC25 phosphatase cleaves inhibitory phosphates and allow CDK to become active.
List the 2 simplified sets of machinery used in regulation of the cell cycle…(these include the cyclins, CDKs…think cell cycles
- G1/S-cyclins & associated CDKs
- G1/S CAKs/CDC25 and Wee1
- SCF (E3 ubiquitin ligase protein complex)
- G1/S-cyclins & associated CDKs
- -M cyclins & associated CDKs
- M CAKs/CDC25 and Wee1
- APC (anaphase promoting complex)
What is the role of Rb protein in the cell cycle regulation?
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.
What does the E2F protein act upon and what are its effects in the cell cycle?
E2F creates more G1/S-cyclin (cyclin E) + S-cyclin (cyclin A) -> activates S-CDK and causes entry into S-[hase (DNA synthesis)
Describe the effect of certain viral proteins acting as competitive inhibitors to Rb binding pocket
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
How does p53 regulate the cell cycle and fulfill its role as the “superhero - guardian of the cell cycle?”
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
What protein usually causes p53 to be degraded by proteasomes? Why does this protein exists?
MDM2.
This protein normally sequesters the constitutively expressed p53 and promotes its ubiqutination and destruction
How does p21 inactivate G1/S complexes
p21 CKI binds to both G1/S cyclin and CDK and inhibits the entire complex
High levels of DNA damage can lead to a very high level of p53. This can cause…?
Apoptosis
What is the point of having the cell arrest in G1 stage if it encounters DNA damage?
Allows cell/ gives the damaged cell time to fix the damage before continuing replication
