Cell Cycle and Nucleus Flashcards
Stages of the cell cycle
G1 (growth)–> S (DNA replication)–> G2 (growth)–> M (mitosis)
Two main checkpoints in cell cycle
G1/S
G2/M
also have a mitotic spindle checkpoint
Questions for G1/ S checkpoint
is the cell big enough?
is the environment good?
is there DNA damage?
G1 / S transition is sensitive to the a) and is b) independent
a) extracellular environment
b) growth factor
What is the irreversible commitment to go through the cell cycle?
G1/ S transition
How does Rb inhibit the G1/ S transition?
Rb can inactivate E2F
(E2F is a transcription factor that increases S-phase gene transcription)
How is Rb inactivated ( thus no longer blocking cell division through the G1/S transition)?
Cyclin/CDK adding phosphate to Rb
Cyclin Kinase Dependent inhibitors (CKIs)
make cyclin/CDK inactive (inhibit cell division)
How does a growth factor act as an extracellular control to affect S phase entry?
growth factor turns on E3 for CKI–> increases CKI degradation–> G1/ S CDK cyclin is then ACTIVE–> adds a phosphate to Rb to make it INACTIVE–> S phase entry
At what point in the cycle is the DNA damage checkpoint? and how does it work?
before S (G1/S transition)
DNA damage tells p53 to become active –> acts a TF to increase expression of CKI –> CKI makes S cyclin/ CDK INACTIVE so there is no phosphorylation of Rb and thus decrease cell cycle/ NO S
Before S what do you use to degrade cyclin?
ubiquination
What questions do you ask at G2 checkpoint?
DNA replicated?
cell big enough?
G2/ M transition
PHOSPHORYLATION is very important (and can turn other proteins on OR off)
If you have active M cyclin/ CDK –> Drives towards mitosis
Describe how MPF (cyclin/ CDK) becomes active
first cyclin binds CDK which makes an inactive MPF, then it gets phosphorylated TWICE by 1) an activating kinase known as CAK) and 2) an inhibitory kinase known as Wee1–> then an ACTIVATING phosphatase known as CDC 25 removes the inhibitory phosphate –> thus the MPF is now active
How does MPF increase its activity so quickly (aka increasing CDK activity all of a sudden)?
positive feedback on the CDC 25
negative feedback on Wee1
What is the point of the mitotic spindle checkpoint?
to tell the cell if it is ready to go from metaphase to anaphase
What do separase, securin and APC do? How do they work in the mitotic spindle checkpoint?
separase–> cleaves cohesion in between sister chromatids (pushes anaphase)
securin–> inhibits separase (keeps it in metaphase)
APC –> is an E3 for cyclin, and turns OFF securin… pushes anaphase
Explain the process of degradation with ubiquination
E1 carries U tag –> E1 E2 E3 form complex –> E1 leaves and passes tag to E2 –> E3 recognizes target protein that needs to be degraded –> E2 passes U to protein and protein gets long U tag that proteasome can come degrade it
What is G0
State of differentiation (NOT dividing), shunted here off G1–> S transition
CKIs upregulated in G0 to keep cyclin/ CDK from being active
Features of nucleus
double membrane (outer is continuous with the ER)
nuclear pore complex
chromatin
nucleolus (make rRNA)
Nuclear lamina
provides structural support inside nucleus (right on edge of inner membrane)
intermediate filaments
A,B, C types
What links nuclear lamina to the cytoskeleton?
Sun/KASH complexes (they span the membrane)
could be microfilaments, microtubules, and intermediate filaments
diff complexes in diff cell types
Nuclear pore complex
traffic IN and OUT of nucleus
BASKET shape
can expand to transport large cargo
What does the long red line point to? The short? where is the view from?
View from cytoplasm.
long line- ribosome
short line- NPCs
