Mod5 - Mechanics of Cell Division Flashcards
What is the class of protein that control the cell cycle (and one specific example)
Cyclin-Dependent Kinases (such as MCdk) - they phosphorylate proteins to control their function
State 2 key things that must happen before mitosis can occur
- DNA must be replicated, and held together by cohesin rings
- Centrosome must duplicate in S-phase (triggered by the same Cdk that controls DNA replication) so that it can nucleate more MTs
Name the three different groups of MTs that form the mitotic spindle
Astral microtubules, Kinetochore microtubules, Interpolar microtubules
What is the function of kinetochore MTs?
They find and attach to kinetochores, and undergo co-ordinated assembly and disassembly during mitosis
What is the function of interpolar MTs?
They grow from one pole and must meet those from the other pole to form anti-parallel interactions
Give a feature of astral MTs and the stage of mitosis they play a crucial role in
They are highly dynamic and play a crucial role in anaphase
How and why do microtubule dynamics increase during mitosis?
Some MAPs are inactivated when phosphorylated by MCdk, and proteins that trigger MT catastrophe are activated in mitosis.
This increases the chance of MTs contacting chromosomes, or MTs from the other centrosome
Name one protein (besides MT Catastrophe Proteins) that is activated by MCdk in mitosis, and what this does
Condensin (causes chromosomes to condense in prophase)
Name one protein (besides MAPs) that is inactivated by MCdk in mitosis, and what this does
Nuclear lamins (causes nuclear envelope to disassemble)
What is the difference between cohesins and condensins?
Cohesins are added when DNA is replicated in S phase, and hold sister chromatids together until anaphase.
Condensins compact the DNA during prophase after being activated by MCdk phosphorylation
What two main processes mark prophase?
Condensation of chromatin, and Formation of the Bipolar Mitotic Spindle via Antiparallel Interactions
Cross-linking by WHICH PROTEIN stabilises interpolar microtubules (and makes them more stable than astral MTs)?
Eg5
What are the roles of Eg5?
Cross-links antiparallel MTs and starts pushing the centromeres apart to form the spindle poles (it is also needed for anaphase)
What are the main things that happen in pro-metaphase?
Nuclear envelope disassembles (and also nuclear lamina in animals); Golgi fragments (causing secretion and endocytosis to stop) so that both daughter cells inherit equal amounts of Golgi
What causes the disassembly of the nuclear lamina in prometaphase?
MCdk phosphorylates nuclear lamins and pore proteins
Define the kinetochore
A specialised protein structure that assembles on to the centromere region of the chromosome during prophase; IT ATTACHES CHROMOSOMES TO MICROTUBULES
What other proteins assist the kinetochore in its function, and what is the “end goal”?
Dyneins and kinesins allow the KC to move along attached MTs in both directions; other proteins act as dynamic linkers between KC and MT plus ends; the goal is for two kinetochores on one chromosome to become attahed to MTs from opposite poles
Describe how tension is involved in mitosis
Kinetochores properly attached to MTs from both poles are under tension (tension is needed before mitosis can proceed)
What 4 things can result in metaphase being blocked?
- Microtubules are depolymerised (e.g., by Nocodazole)
- Microtubules are stabilised (e.g., by taxol)
- Spindle hasn’t assembled properly (e.g., monastrol inhibiting Eg5)
- If any kinetochores are not attached to the spindle
What is the complex that generates the “stop signal” to delay anaphase, and what is the name of the specific protein kinase within the complex?
Spindle Assembly Checkpoint (SAC) complex; Mad2
What happens when the last kinetochore is attached to the MT that allows anaphase to proceed?
The SAC is removed from the kinetochores by dynein, so APC is no longer inhibited
How does SAC actually prevent anaphase from starting?
The active SAC complex at the kinetochore activates a cytosolic pool of APC INHIBITOR COMPLEX that inhibits APC
What is APC and what is its main function?
Anaphase promoting complex; it triggers proteolysis of securin (and cyclin B) by covalently attaching ubiquitin
What is the result of APC triggering degradation of securin?
Separase enzyme is no longer inhibited, so it cleaves cohesins, which then dissociate, allowing anaphase to take place
How much do the various stages of mitosis vary between cells in the same population?
Prometaphase varies a lot (due to the Metaphase checkpoint); all other stages are fairly similar
What problem can result from early entry into anaphase or premature securin degradation?
Aneuploidy due to defective mitosis (sister chromatids come apart before anaphase)
What happens during the two sub-phases of anaphase?
Anaphase A = sister chromatids move towards the spindle poles
Anaphase B = spindle poles move further apart
How do sister chromatids move towards the poles during Anaphase A?
By remaining attached to depolymerising kinetochore microtubules
What two forces move the spindle poles further apart in Anaphase B?
- A sliding force between interpolar microtubules from opposite poles - this PUSHES poles apart
- a PULLING force at the cell cortex drags the two poles apart
Describe the role of Eg5 in Anaphase B
Eg5 cross-links antiparallel MTs and pushes the centrosomes apart
Describe the role of tubulin in Anaphase B
Interpolar MTs keep growing by addition of tubulin dimers at MT plus ends
Describe the pulling forces from the cell cortex during Anaphase B?
Dynein anchored in the cell cortex pulls on astral MTs
What are the three main events that occur during telophase?
- Nuclear envelope and nuclear lamins reassemble
- Golgi apparatus starts to reassemble
- Secretion and endocytosis restart
In Cytokinesis, what defines WHERE the cleavage furrow assembles and the cell will divide?
The central spindle (i.e., the antiparallel region) recruits and activates proteins that signal to the cortex to start contractile ring assembly
What is different about the actin and myosin in the contractile ring compared to muscle?
They are dynamic, allowing the ring to get smaller over time and eventually pinch off the two daughter cells
What is different about metaphase and anaphase in plant cells?
They do not have centromeres or dynein; spindle poles are broad and organised by minus-end-directed kinesins
[Overview/What-is-different] for telophase and cytokinesis in plant cells?
Plant cells divide by making a new cell membrane, then a new cell wall. This process needs Golgi-derived vesicles and microtubules, NOT ACTIN AND MYOSIN
