Mechanics Of Cell Division Flashcards
What is the main purpose of cell division?
To allow growth, repair, and reproduction of cells
Cell division is essential for the maintenance of life in multicellular organisms.
What are the phases of the eukaryotic cell cycle?
G1, S, G2, M
G1 is the gap phase before DNA synthesis, S is the phase of DNA replication, G2 is the gap phase before mitosis, and M is mitosis.
What triggers cell cycle entry?
Mitogens
Mitogens are substances that stimulate cell division.
What are oncogenes?
Mutated genes that promote cancer
Oncogenes can lead to uncontrolled cell proliferation.
What role do tumour suppressor genes play in cancer?
They inhibit cell division and prevent tumor formation
Loss of function in these genes can contribute to cancer development.
What is the role of M-Cdk1/cyclinB in mitosis?
Controls and coordinates mitosis through phosphorylation
M-Cdk1/cyclinB is crucial for the progression of the cell cycle.
What happens during the prophase of mitosis?
- Chromosomes condense as condensins compact the DNA
- Condensins are activated by M-Cdk phosphorylation
- Cohesin rings hold sister chromatids together until anaphase
- Bipolar mitotic spindle starts to form —> MTs growing from the 2 centrosomes meet and start to interact via antiparallel interactions = this overlap zone drives pole separation
How is cytokinesis different in plant and animal cells?
Animal cells form a cleavage furrow (a contractile ring of actin & myosin filaments), while plant cells form a cell plate.
What is the function of cohesin during the cell cycle?
Holds sister chromatids together until anaphase
Cohesin is crucial for the accurate segregation of chromosomes.
What is the significance of the spindle assembly checkpoint?
Ensures proper attachment of chromosomes to the spindle before anaphase
This checkpoint prevents errors in chromosome segregation.
Fill in the blank: The _______ is a specialized protein structure that assembles on the centromere region of the chromosome in prophase.
kinetochore
What are the three types of microtubules involved in the mitotic spindle?
- Kinetochore microtubules —> MTs have to find and attach to these, they must be able to undergo coordinated assembly and disassembly
- Interpolar microtubules —> MTs growing from one pole must meet those from the other pole and form antiparallel interactions
- Astral microtubules —> are highly dynamic and play a crucial role in anaphase
True or False: The nuclear envelope disassembles during prophase.
False
The nuclear envelope disassembles during prometaphase.
What is the role of Eg5 in prophase of mitosis?
Cross-links anti-parallel microtubules and pushes centrosomes apart to form the spindle poles
Also required for anaphase & prometaphase
What is a major driver of chromosome movement during mitosis?
Microtubule assembly and disassembly
This dynamic process is essential for the accurate segregation of chromosomes.
Describe the changes in membrane dynamics during M-phase.
- Nuclear envelope disassembles
- Golgi apparatus fragments
- Membrane traffic stops
These changes facilitate the separation of chromosomes and the formation of daughter cells.
What is the consequence of phosphorylation by M-Cdk?
Phosphorylation activates
- Condensin —> chromosomes condense (prophase)
- Microtubule catastrophe proteins —> MTs more dynamic
Phosphorylation inactivates
- MAPs —> MTs more dynamic
- Nuclear lamins —> nuclear envelope disassembles
Fill in the blank: The _______ checkpoint monitors tension across chromosomes to control the exit from metaphase.
spindle assembly
What happens to microtubules during anaphase?
They undergo coordinated assembly and disassembly to separate sister chromatids
This dynamic behavior is critical for accurate chromosome segregation.
What does phosphorylation control?
- cell growth
- gene expression
- cell cycle
- cell survival
- metabolism
- cell division
Role of Cdks
Phosphorylate key proteins to control their function in the cell cycle
Structure of Cdks
Key things that must occur before mitosis
- Interphase (G2) —> cells increase in size
- S phase —> DNA of chromosomes is replicated and centrosome is duplicates, organelles must grow
- Cohesin rings are added when DNA is replicated in S phase and holds sister chromatids together until anaphase
Centrosome duplication in S phase
- Centrosomes are a focus for Microtubule polymerisation
- These duplicate in S phase = triggered by the Cdk that controls DNA replication
- Duplicated centrosomes need to separate = 2 spindle poles
- Centrosome nucleates more Microtubules in mitosis
- Each daughter cell gets a centrosome after cytokinesis
Set up of the mitotic spindle
- Number of Microtubules nucleated by the centrosomes increases from prophase
- Microtubules are more dynamic
- They switch from growing to shrinking more often = catastrophe
Why do dynamics increase in the mitotic spindle?
- Some MAPs are inactivated when phosphorylated by the mitotic kinase M-Cdk
- Proteins that trigger Microtubule catastrophe are activated in mitosis
- This results in a greater chance of MTs growing from each centrosome contacting each other or chromosomes
Role of Eg5 in the bipolar spindle formation
- Antiparallel interactions are mediated by Eg5 = stabilises the MTs
- Eg5 inhibition prevents centrosomes from separating in prophase and prometaphase
- forms monopolar spindle
Describe prophase
- Chromosomes condense because condensins compact the DNA (M-Cdk)
- Duplicated centrosomes start to separate forming 2 spindle poles. Eg5 is needed here where the MTs overlap
- Centrosomes nucleate more MTs by M-Cdk
- The mitotic spindle starts to form, starting with the interpolar MTs
What happens in prometaphase?
- Nuclear envelope disassembles
- Nuclear lamina disassembles in animal cells
- Nuclear envelope disassembles in plants
- Nuclear envelope and lamins reassemble in telophase
Role of nuclear lamins
Are M-Cdk substrates
What happens in the Golgi apparatus in prometaphase?
Fragments so that each daughter cell will inherit equal amounts of Golgi apparatus membranes
Secretion and endocytosis stop
What happens in the transition from prophase to prometaphase?
- Nuclear envelope, nuclear lamina and Golgi apparatus disassemble
- Secretion and endocytosis stop
- Nuclear envelope disassembly allows MTs to interact with chromosomes
- More MTs are nucleated by the centrosome from prophase onwards
- MTs are more dynamic
- Results in a greater chance of MTs growing from each centrosome contacting chromosomes quickly
Role of kinetochores
- Specialised protein structure that assembles onto the centromere region of the chromosome in prophase
- Attaches chromosomes to MTs by a dynamic linker that holds onto the MT
- Kinetochores can move along MTs in both directions using MT motors
- Other proteins act as dynamic linkers between kinetochores and MT plus ends, even when the MT is growing and shrinking
- MTs attached to kinetochores grow and shrink in a co-ordinated way
Microtubule dynamics at the kinetochores
- Multiple MTs at each kinetochore must grow or shrink together
- MT assembly and disassembly is a major driver of chromosome movement
- MT motors also play a role
Crucial properties of the kinetochore
- Specialised chromosomal structure needed for spindle attachment
- Binds multiple MTs at once
- MT bundles attached to the kinetochore can switch between growing and shrinking in a regulated way
- Move in both directions along MTs by harnessing MT assembly & disassembly and using MT motors
- Kinetochores properly attached to MTs from both poles are under tension
- Tension is needed before mitosis can proceed
Direction of chromosome movement
Constantly changes until anaphase
What happens to chromosomes during metaphase?
Chromosomes align in the middle of the spindle and are attached to spindle via kinetochores with 1 kinetochore at each pole
Kinetochores can move in either direction by harnessing microtubule dynamics and motors
What is the role of the metaphase checkpoint?
It blocks the transition from metaphase to anaphase if certain conditions are not met
Conditions include depolymerised microtubules, improperly assembled spindle, or unattached kinetochores
What is the outcome if the metaphase checkpoint is functioning correctly?
Each cell waits for all chromosomes to align before transitioning to anaphase
Duration of prometaphase can vary significantly among different cells
What is the master regulator of mitosis during the metaphase to anaphase transition?
M-Cdk is active during metaphase and turned off during anaphase
This regulation is crucial for the separation of sister chromatids
What triggers the transition from metaphase to anaphase?
Activation of the anaphase promoting complex (APC/C)
APC/C triggers proteolysis of cyclin B and securin, leading to activation of separase
What happens during Anaphase A?
Sister chromatids move towards the spindle poles by staying attached to depolymerising kinetochore MTs
What occurs during Anaphase B?
- Kinesin Eg5 required to set up the bipolar spindle
- Eg5 cross links antiparallel MTs and pushes the centrosomes apart
- Interpolar MTs continue growing = get longer by addition if tubulin dimers at MT plus ends
- Dynein anchored at the cell cortex pulls on the Astral MTs
What are the specific events that occur during telophase?
Reassembly of nuclear envelope, reassembly of Golgi apparatus, restart of secretion and endocytosis
The genome is already equally separated before telophase
What defines where the cleavage furrow assembles during cytokinesis in animal cells?
The central spindle recruits and activates proteins that signal to the cortex to start contractile ring assembly in anaphase/telophase
Actin and myosin filaments are very dynamic and the contractile ring gets smaller over time
What is the main difference between cytokinesis in animal and plant cells?
Animal cells use actin and myosin, while plant cells use Golgi-derived vesicles and microtubules
Plant cells do not have centrosomes or dynein
What is the role of dynein in mitosis?
Dynein anchors at the cell cortex and pulls on astral microtubules
This contributes to the separation of spindle poles
What happens if a single kinetochore is not attached to the spindle?
The transition to anaphase is blocked, and a stop signal is generated
This is part of the spindle assembly checkpoint mechanism
Fill in the blank: The anaphase promoting complex triggers proteolysis of __________ and __________.
cyclin B and securin
True or False: The metaphase to anaphase transition is loosely controlled.
False
It is very tightly controlled by the spindle assembly checkpoint
What happens if problems at the metaphase checkpoint cannot be corrected?
The cell undergoes apoptosis
This prevents the propagation of cells with incorrect chromosome numbers
What is the role of cohesins during mitosis?
Cohesins hold sister chromatids together until they are cleaved at anaphase
This cleavage is crucial for allowing sister chromatids to separate
What blocks the transition from metaphase to anaphase?
- MTs are depolymerised (e.g. using drug nocodazole)
- MTs are stabilised (e.g. using taxol)
- Spindle hasn’t assembled properly (e.g. by inhibiting Eg5 with monastrol)
- If a single kinetochore is not attached to the spindle
What happens when chromosomes are unaligned?
- Kinetochores unattached
- STOP signal generated by the spindle assembly checkpoint complex (SAC) at the Kinetochore (KT)
- Anaphase is delayed
If chromosomes are aligned, KTs remain attached and SAC protein are removed from KTs by cytoplasmic dynein = no stop signal and all clear for anaphase
Consequences of entering anaphase too early
Anueploidy - wrong number of chromosomes
What happens in the transition from metaphase to anaphase?
- Master regulator of mitosis is active (M-Cdk)
- Sister chromatids are held together by cohesins
- Chromosomes are aligned so SAC is off
- APC/C is active (anaphase promoting complex)
- A protease seperase is activated
- M-Cdk is turned off
- Sister chromatids come apart as cohesins are cleaved
How is the metaphase to anaphase transition controlled?
- chromosomes are replicated in S phase to give 2 sister chromatids
- after replication, sister chromatids stick together via cohesins
- at anaphase, they separate as cohesins are cleaved by separase
Role of APC/C
Triggers proteolysis of specific proteins
- Covalently attaches ubiquitin
- Ubiquitin tagging directs proteins to the proteasome for degradation of cyclin
Key substrates are Cyclin B subunit of M-Cdk and Securin (a separase inhibitor)
When SAC is active
- stops sister chromatids coming apart
- keeps the cell in metaphase by maintaining M-Cdk activity
2 phases of anaphase
Anaphase A = sister chromatids move towards the spindle poles
Anaphase B = spindle poles move further apart
How does animal cell morphology change through mitosis?
- Cells become rounded and less well attached to the surface whilst dividing
- Actin & myosin filaments are drastically rearranged
- Integrins are phosphorylated and weaken their grip on the extracellular matrix
Cell division in plant cells
- plant cells do not have centrosomes or dynein
- their spindle poles are broad and organised by minus-end-directed Kinesins
Telophase & cytokinesis in plant cells
- Plants and algal cells divide by making a new cell membrane then a new cell wall
- Needs Golgi-derived vesicles and MTs (not actin and myosin)
