Week 8 the eukaryotic cell cycle, mitosis and apoptosis Flashcards
Cell division
Allows the continuity of life
Cell cycle
Series of cyclic events for cell duplication and division, essential for all living things to reproduce and grow
In unicellular organisms
Each cell division produces a new organism
Cell cycle in Eukaryotic cells
4 Phases:
1)G1 phase
2)S phase (DNA replication)
3)G2 phase
G1 -> S -> G2 -> interphase
4)M phase, comprising of;
-mitosis (nucleus division)
-cytokinesis (cytoplasm division)
Cell division rates
Not all cell types divide and cell division rates are different between cells
Non-dividing cells are in a quiescent state, called G0 phase
Cell cycle control system
Uncontrolled cell division can result in cancer
The cell-cycle control system regulates the normal progression of the cell cycle
It occurs at 3 cell cycles transition checkpoints…
It occurs at 3 cell cycles transition checkpoints
(G1/S, G2/M & metaphase/anaphase checkpoints)
Cell cycle control system roles
It ensures that all the events required in each phase are completed before the next one begins
If not;
-It halts the cell cycle
-Or enters the G0 resting phase (outside the cell)
-Or activates apoptosis
Cdks
Progression at checkpoints depends on the cyclical activation of distinct proteins,
Cyclin-dependent kinases (Cdks), when associated to regulatory proteins, cyclins
Cdk activation
Cdks require interaction with specific cyclins to become active
->Cyclins regulate the activation of CDKs
Cdks are also phosphorylated to be active
Activated Cdks phosphorylate target proteins to drive cell cycle progression
Cdk activation
Cdks require interaction with specific cyclins to become active
->Cyclins regulate the activation of CDKs
Cdks are also phosphorylated to be active
Activated Cdks phosphorylate target proteins to drive cell cycle progression
Different Cyclin–Cdk complex levels
Distinct cyclin–Cdk complexes control various cell cycle phases (G1, S, G2, M)
->Transition through checkpoints is irreversible
->4 different cyclins are synthesised in response of specific signals and degraded after the cell progresses past the corresponding checkpoint
->CDKs are not destroyed, but cyclically activated/deactivated by phosphorylation / dephosphorylation
Different cyclin–Cdk complex levels
Distinct cyclin–Cdk complexes control various cell cycle phases (G1, S, G2, M)
->Transition through checkpoints is irreversible
->4 different cyclins are synthesised in response of specific signals and degraded after the cell progresses past the corresponding checkpoint
->CDKs are not destroyed, but cyclically activated/deactivated byphosphorylation /
dephosphorylation
G1 phase
Period of metabolic activity, cell growth, and general repair to prepare the cell for division
G1 phase
Period of metabolic activity, cell growth, and general repair to prepare the cell for division
G1/S checkpoint
The cell assesses DNA integrity and determines if conditions are favourable to progress into cell cycle
G1/S checkpoint
The cell assesses DNA integrity and determines if conditions are favourable to progress into cell cycle
checkpoint G1-to-S transition - key decisions
->Proceed to S Phase: Triggered by extracellular signals (mitogens) → good conditions
Delay S Phase Entry: Allows for further growth or DNA repair
->Exit the cell cycle by entering the G0 Phase: Can occur temporarily or permanently
->Initiate Apoptosis (programmed cell death): A response to severe DNA damage
Checkpoint G1-to-S transition - key decisions
->Proceed to S Phase: Triggered by extracellular signals (mitogens) → good conditions
->Delay S Phase Entry: Allows for further growth or DNA repair
->Exit the cell cycle by entering the G0 Phase: Can occur temporarily or permanently
->Initiate Apoptosis (programmed cell death): A response to severe DNA damage
S phase
In the S phase, each chromosome (nuclear
DNA) is replicated - DNA synthesis
->S-Cdk activates helicases and other enzymes to initiate DNA replication
->Chromosomes are not yet visible in their X-shape; they exist as chromatin
In S phase, centrosome is also duplicated
S phase
In the S phase, each chromosome (nuclear DNA) is replicated - DNA synthesis
->S-Cdk activates helicases and other enzymes to initiate DNA replication
Chromosomes are not yet visible in their X-shape; they exist as chromatin
In S phase, centrosome is also duplicated
Centrosome
Is a cellular structure that controls the microtubules organisation within the cell
Composed of 2 centrioles
(9 triplets of microtubules)
Centrosome
Is a cellular structure that controls the microtubules organisation within the cell
-Composed of two centrioles
(9 triplets of microtubules)
Centrosome main functions;
->Facilitates the assembly / disassembly of microtubules to arrange cytoskeleton
->It organises microtubules during cell division to form the mitotic spindle
-The mitotic spindle ensures accurate chromosome segregation in mitosis
Centrosome main functions;
->Facilitates the assembly /
disassembly of microtubules to arrange cytoskeleton
->It organises microtubules during cell division to form the mitotic spindle
-The mitotic spindle ensures accurate chromosome
segregation in mitosis
G2 phase
Rapid cell growth and protein synthesis (enzymes) in preparation for mitosis
Thorough check for unreplicated/damaged DNA
G2 phase
Rapid cell growth and protein synthesis (enzymes) in preparation for mitosis
Thorough check for unreplicated / damaged DNA
Checkpoint end of G2/entry into mitosis
->If DNA is fully replicated and not damaged, proteins involved in early mitosis are activated, allowing the cell to enter mitosis
->Incomplete replication can arrest the cell cycle
Checkpoint end of G2/entry into mitosis
->If DNA is fully replicated and not damaged, proteins involved in early mitosis are activated, allowing the cell to enter mitosis
->Incomplete replication can arrest the cell cycle
M Phase Overview
Cell division is a continuous sequence of events (5 stages), usually symmetric;
1)Prophase
2)Prometaphase
3)Metaphase
4)Anaphase
5)Telophase
Comprised of mitosis and cytokinesis
M Phase Overview
Cell division is a continuous sequence of events (5 stages), usually symmetric
Stage 1 - Prophase
Chromatin is condensed into
visible chromosomes (by condensins)
All the nuclear activities are ceased
Outside the nucleus, the mitotic spindle assembles between the two duplicated centrosomes, which have begun to move apart
Stage 1 : Prophase
->Chromatin is condensed into
visible chromosomes
(by condensins)
->All the nuclear activities are ceased
->Outside the nucleus, the mitotic spindle assembles
between the two duplicated centrosomes, which have begun to move apart
Stage 2 : Prometaphase
->Nuclear envelope disintegrates
->The 2 centrosomes are at the spindle poles (opposite ends) of the cell
->Chromosomes are attached to spindle microtubules of one pole via their kinetochores (protein complexes of the chromosomes’ centromere on both chromatids)
Stage 3 : Metaphase
->Mitotic spindle is fully developed
->Kinetochores on each sister chromatid attach to opposite poles of the spindle
->The chromosomes are aligned at the spindle equator (midway between poles)
->M checkpoint controls the proper chromosomes alignment and attachment
Stage 4 : Anaphase
->Cohesins, holding sister chromatids together, break down → X-shaped chromosomes
->Sister chromatids of each chromosome segregate (now individual chromosomes) and are pulled toward the opposite spindle poles
-Because kinetochore microtubules shorten and the spindle poles also move apart
Stage 5 : Telophase
->The two sets of chromosomes arrive at the spindle poles and decondense
->Nuclear envelopes and lamina reassembles around each set of chromosomes, formation of two nuclei → final event of mitosis
It starts the cytoplasm division → formation of the contractile ring, between poles
Stage 6 : Cytokinesis
The cytoplasm is divided in two by the contraction of contractile ring, which
pinches the cell into two daughters → each with one nucleus (same DNA)
M phase overview
Prophase: condensation of chromosomes; starting formation of two poles
Prometaphase: nuclear envelope breakdown; chromosomes attachment to spindle microtubules
Metaphase: chromosomes aligned at the equator (midway) of the spindle
Anaphase: sister chromatids separated; moving to the two poles
Telophase: reformation of nuclear envelopes (nuclear separation), formation of contractile ring
Cytokinesis: separation of two daughter cells
Apoptosis
Programmed cell death induced by external and internal stimuli
e.g.,
-Removing cells during embryonic development
-Cells no longer needed
-Cells with severe DNA damage
-Cells infected by viruses (preventing damage to neighbouring cells)
Different from other cell death processes, like Necrosis (death due to acute injury) -> non controlled event, causing cell rupture and leakage outside → inflammation
Apoptosis activation
Internal and external signals activate a proteolytic cascade mediated by proteases (cleaving
peptide bonds of proteins) switching from procaspases (inactive) into caspases (active)
Intrinsic pathway
An intracellular signal in response to stress -> radiations, heat, viral infection
->Altering the permeability of
mitochondrial outer membrane that release cytochrome c from
intermembrane space into the cytosol
->Cytosolic cytochrome c induces procaspases activation into caspases
External pathway
Exposure of a extracellular death signal (Fas ligand) from a different cell
Each cell has ‘death receptors’ on its surface
Ligand-receptor binding recruits and activate procaspases into active caspases
Apoptosis & caspases
Both pathways activate initiator caspases
Initiator caspases cleave, and activate, downstream caspases, which break down key proteins (e.g. enzymes, structural proteins) to kill the cell quickly and neatly (no leakage outside)
->Cytoskeleton collapses
->The nuclear envelope disassembles
->The nuclear DNA breaks up into fragments
->Cell shrinkage
Survival factors promoting cell survival and suppress apoptosis
Apoptosis and health
The rate of cells dying should balance the rate of cells produced by mitosis
Apoptosis plays a role in maintaining the correct balance
Insufficient apoptosis
Leads to the formation of
tumours
Cancer cells acquire mutations allow them to escape apoptosis
(cancer hallmark)
Excessive apoptosis
Leads to cell loss and
degeneration
