Topic 9: Cell Cycle Flashcards
List and describe the stages of the cell cycle and the time it takes
G knot: cell is stationary and not in the process of anything
G1: growing (9 hours)
S: DNA replication and repair (10 hours)
G2: growing (4.5 hours)
M: division of cells (30 minutes)
what factors drives each stage to each stage
G0 to G1:
G1 to S: growth factors, nutrients, cell size, DNA damage
S to G2: no factors, moves there when done synthesizing
G2 to M: Cell size, DNA damage and replication
M to cytokenisis (chromosome attachment to spindle)
what is the order of the Cdk complexes?
G1-Cdk complex
G1-S Cdk complex
S-Cdk complex
M-Cdk complex
what is the role of Cdk?
(cyclin dependant kinase) they are expressed consistently throughout the cell cycle and only become activate when their cyclin binds totem allowing them to control the cell activity
what is the role of Cyclins?
they increase in expression when they need activate the Cdks of that stage so they can control the activity of the cell
what are the cyclins and Cdk involved in the mid G1-Cdk complex?
Cyclin D and Cdk4&6
what are the cyclins and Cdk involved in the G1-S Cdk complex?
Cyclin E & Cdk2
what are the cyclins and Cdk involved in the S-Cdk complex?
Cyclin A and Cdk2
what are the cyclins and Cdk involved in the M-Cdk complex?
Cyclin A & B and Cdk 1&2
how does a cyclin activate a CDK? (steps)
1) The cyclin binds to the Cdk and the T loop of the Cdk goes into the cyclin
2) the Cak (Cdk activating kinase) adds a phosphate on the Thr residue to activate the complex
3) at the same time the Wee1 (Cdk-inhibiting kinase) adds an extra phosphate on the Tyr residue to inhibit the complex
4) then the activated Cdc25 comes and removes the phosphate again so the complex becomes active
explain the positive feedbacks of the Cdk Activation
1) the active Cdk phosphoylates the Cdc25 phosphatase
2) the active Cdk stops the Wee1 from adding its inhibitory phosphate because it wants to stay activate
how can cyclin and cdk activity be inhibited and what are some examples?
an inhibitor called p27 (usually in the s phase) pulls part the active complex
p21 will do the dame in s phase if it detects DNA damage
how are cyclins and CKI regulated?
It is when the polyubiquitylation chain gets added to the complex tagging to be degraded by a proteasome
- called proteolysis
how does M-cdk trigger mitosis and what events does it regulate?
the accumulation of M-Cdk after G2 triggers the
- chromsome condensation: pack so its easier to divide
- phorsphorlaytion of nuclear lamins: breaks the nuclear envelope
- spindle formation
- chromosome separation
how does chromosome condensation occur?
protein called condensin (5 subunit with 2 SMC subunits) uses ATP to loop the DNA strands and tighten them
how does the mitotic Cdk promote spindle formation?
it phosphorylates kinesin 5 motor proteins to activate kinetochore microtubules and stimulates centrosome separation
- the kinetochores are the ones that attach to the centrosome of the sister chromatids
- kinetochore have 16 proteins at the centrosome
why is it important for stable chromosome attachment to the kinetochores
so there is an even divide of the DNA in each daughter cell
what is the key regulator of the transition form metaphase to anaphase?
all the chromosomes being attached to their kinetochores, then cdc20 activates APC/C
when does Cdc20 get synthesized and how does it get activated?
it gets synthesized as the cell reaches mitosis and it gets activated by M-Cdk
why is APC/C and what does it allow?
APC/C complex is an ubiquitin ligase family of enzymes that catalyzes the ubiquitiination and degradation of
- serurin
- Mitotic cyclin
What happens when securin is destroyed?
it activates separase and that destroys the cohesion that keep the chromatins together so anaphase can occur
how is mitotic cylcin destroyed and what controls it?
- Cdc20 and a factor called Cdh1 makes APC kill the m cyclin
- cdh1 gets activated in late anaphase and is regulated by G1cylin/cdk complex
what is the key factor that allows exit of mitosis
Cdc14 must dephosphorlyate Cdh1
what is the mechanism for regulation of the G1/S transition
the restriction point: the point of no return, mitogens are no longer needed to reach S phase
