Cellular Reproduction: The Cell Cycle (3) Flashcards
cell cycle
time from one division to the next division
how is the cell cycle divided?
2 phases: M phase & interphase
interphase
cell growth & metabolism
what causes the variation in duration of interphase?
depends on cell type
what are the categories that we did cells into in the cell cycle?
- cells that don’t cycle but enter a permanent arrest stage, once differentiated remain in that state until they die (ex: neurons, muscle cells, RBCs)
- Cells that normally don’t divide but can be induced (ex: liver, lymphocytes)
- Cells that divide regularly (ex: epithelial cells)
why do RBCs lack a nucleus?
no longer necessary since they will no longer be dividing
what controls cell division?
cytoplasmic factors
what was the experiment to find what controls the cell cycle?
fused mitotic & interphase cells
interphase cells in G1 had premature condensed c’some & attempted M phase (the non mitotic cell)
concluded that there is a factor in the mitotic cell that directs cells to undergo mitosis
what controls the cell cycle at the G2/M transition?
maturation promoting factor
entry into mitosis requires this PRO complex
what is MPF?
complex of 2 PROs:
cyclin b: regulates cdK1 activity, levels rise & fall through the cell cycle
Cdk1: kinase added a phosphate tot other PROs, modifying the target’s PROs activity (cyclin dependent kinase)
when is there first an increase in cyclin b?
G2
when does cyclin b peak? and when does it drop?
M phase & at the end of M phase
what is the role of MPF?
phosphorylates & activates PROs of mitosis
when are cyclins not produced?
G0
What are some MPF functions?
activates lamin PROs, causing the nuclear envelope to break (dissociates PRO from membrane)
alters DNA bound PROs (histones) causing DNA to condense. During Prophase enabling c’some to travel to poles
activates PROs of the mitotic spindle in pro prometaphase
Wee1 PRO & what happens when the mutant lacks it
inhibitor of MPF
results in early cell division (enters too early), smaller daughter cells than what they should be
Cdc25 PRO & what happens when the mutant lacks it
activates MPF
division fails too occur, large cell
how does cdc25 activate cdk?
Removes phosphate form Tyr15 activating cdk
what inhibits MPF activity?
wee1 adds phosphate to Try 15
CAK
cyclin activating kinase
adds P to Thr161, when removed mitosis is terminated
activates Cdk1
What happens when P is removed from Thr161?
cyclin detaches & degraded, ends mitosis
what activates Cdk1?
CAK adds P on Thr161
once removed mitosis ends
what inactivates Cdk1?
wee1 phosphate on Tyr15
how is cyclin action turned off?
activation of ubiquitin ligase
ubiquitin ligase
terminates MPF activity
Attaches ubiquitin to cyclin tagging it for destruction by causing proteolysis
What does MPF phosphorylate?
lamin
histones
microtubules
ubiquitin ligase
When are cyclins & cdk1 low?
G1
proteasome
proteolysis of cyclin terminating MPF activity
What is necessary to work at G0 to have successful mitosis?
if wee1 isn’t working the cells go on too soon & end up small
What are the MPF checkpoints & end do they occur?
Metaphase checkpoint:
o M phase
o Chromosomes aligned?
Start or restriction checkpoint:
o End of G1
o Cell decides whether to continue or not Cell big enough? Envr okay? DNA okay?
G2 checkpoint:
o G2
o DNA intact post replication?
Will not attempt division if DNA is damaged
MPF checkpoint:
o End of G2
o DNA replicated? Cell big enough? Does it have enough stuff?
What is the result of the DNA damage checkpoint in G1 not functioning properly?
Ataxia-telangiectasia (AT)
PROs involved in DNA repair fail indivs with AT
prone to cancer:
Ionizing radiation (ATM PRO) - breaks DNA
Ultraviolet radiation (ATR PRO)
What are the steps in the checkpoint if there is DNA damage?
- ATM detects break in DNA in G1
- ATM phosphorylates Chk2 activating it
- Chk2 phosphorylates p53
- Phosphorylated p53 activates gene p21 (gene is synthesized)
- P21 PRO binds to Cdk (inhibition)
cell prevented from entering S phase until DNA is repaired
ATM PRO role
detects break in DNA in G1
Chk2
kinase
phosphorylates p53 in cell damage checkpoint
p53 role
when phosphorylated, turns on p21 gene causing its synthesis
p21
gene synthesized when there is damage in DNA, PRO inhibits Cdk
50% of human tumor cells have mutations in which gene?
p53
what are the 3 components of a checkpoint?
- Sensor –> is DNA damaged? (ex: ATM/ATR PROs)
- Transducer: create a signal, enables the cell to work in a multi-step fashion, diff controls systems interact (ex: Cdc25, p53, MPF PROs)
- Effector: change key enzyme action/PRO (ex: P21, phosphorylated lamins, histones, ubiquitin etc.)
What is the effector in then DNA damage checkpoint?
P21
What are the checkpoints in the cell cycle?
- Progression from G2 to M by the MPF
- Checkpoints for DNA damage in G2 + G1 (before & after rep) –> cell cycle halts allowing time for repair
- Spindle checkpoint in M phase
