The eukaryotic cell cycle & interphase Flashcards
Cell division
continuity of life
Why is duplication and cell division so important?
Cell cycle
- essential mechanism by which all living things reproduce/grow
e.g unicellular organisms, each cell division produces a new organism
rounds of cell divisions are required from the fertilised egg cell to develop into multicellular organisms
How often do cells divide?
-not all cells divide
-rates are different in different cells
-highly specialised cells (muscle and nerve cells) do not/rarely divide
-epithelial cells in gut divide x2 a day
-liver cells only one in a year/two
Resting state
when cells reach certain size, growth either stops its cycle or cell MUST divide
Eukaryotic cell cycle - phases?
M phase
G1 phase
S phase (DNA replication)
G2 phase
(non-dividing cells are usually reversible) state - G0 phase or RESTING PHASE (of the replicative cell cycle)
Why does cell division have to be controlled?
To avoid uncontrollable cells division - CANCER
checkpoints in cycle…
biochemical switches - to pause the cycle at 3 main transition points
Cdks
Cyclically activated Cyclin-dependent protein kinases
How does Cdks come active?
must bind to a specific regulatory protein called cyclin
(cdks must be in a particular phosphorylation state)
do cyclins have enzymatic activity?
No
G1 phase
Period of metabolic activity, cell growth, and
general repair. The cell grows in mass to
prepare the cell for division
To pass the checkpoint, according to
- Cell size
- Presence of nutrients, grow factors
- DNA integrity
Cells can …… in G1 phase
- Proceed to S phase; extracellular signals(mitogens) induces progression
- Delay the entrance in S phase (to further grow or if DNA is damaged)
- Exit the cell cycle to G0 (temporarily or permanently)
- Induce a programmed cell death (apoptosis), if there is a severe DNA damage
checkpoint
G1-to-S
DNA replication
Process by which DNA makes a copy of itself
DNA must rapidly and accurately copy (replicate) its nucleotide sequence (to avoid
mistakes/mutations)
During DNA replication
46 chromosomes (in form of chromatin) forms two identical duplicated DNA molecules (x2 sister chromatids - joined at centreomere)
S phase
DNA is replicated, therefore this phase is highly regulated
What happens immediately in S phase?
Once entered into the S phase, S-Cdk activates
helicases and other proteins to form the replication
forks and initiate the DNA replication
Duplicated chromosome
Sister chromatids are connected by cohesins (for chromosome segregation
In s phase - centrosome is also duplicated
Centrosome
Cellular structure that controls location, number and orientation of microtubles
Centrosome structure?
Composed of 2 centrioles (9 triplets of microtubules)
G2 phase
- Rapid cell growth and protein synthesis
(accumulation of enzymes) to prepare for mitosis - To check for unreplicated or damaged DNA
Checkpoint end of G2/ entry into mitosis
- If DNA is fully replicated and not damaged, proteins involved in early mitosis are
activated and the cell enters in mitosis (onset of prophase) - Incomplete replication can arrest the cell cycle
M phase
Cell division is a continuous sequence of events (5 stages), usually symmetric
M phase key points:
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
Stage 1 - prophase
- Chromatin is condensed into visible chromosomes (by condensins)
- Transcription activities ceased
Outside the nucleus, the mitotic spindle assembles between the two centrosomes,
which have begun to move apart
Stage 2 - Prometaphase
- Nuclear envelope and nuclear lamina breakdown
- The 2 centrosomes are now at the 2 spindle poles (opposite ends) of the cell
- Chromosomes attach 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
- The chromosomes are aligned at the spindle equator (midway), between poles
- Kinetochores on each sister chromatid attach to opposite poles of the spindle
- M checkpoint controls the proper chromosomes alignment and attachment
Stage 4 - Anaphase
- Cohesins, which kept sister chromatids together, break down
- Sister chromatids synchronously separate (now individual chromosomes) and are pulled slowly toward the opposite spindle poles to which they are attached
- Kinetochore microtubules shorten and the spindle poles also move apart
Sage 5 - Telophase
- The two sets of chromosomes arrive at the spindle poles and decondense
- A new nuclear envelope and nuclear lamina reassembles around each set of chromosomes, completing the formation of two nuclei (end event of mitosis)
- It starts the division of the cytoplasm with the formation and contraction of the contractile ring (actin and myosin), at midway between the spindle poles
Stage 6 - Cytocynesis
- The cytoplasm is divided in two by a contractile ring, which pinches the cell into two daughters, each with one nucleus (same DNA).
- The mitotic spindle determines the plane of cytoplasmic cleavage
Programmed cell death (Apoptosis)
Apoptosis is a form of programmed cell death induced by external and internal stimuli
Removing cells during embryonic development (fingers/toes formation)
Cells no longer needed
Cells with severe DNA damage
Cells infected by viruses (preventing damage to neighbouring cells)
Necrosis - cells dying for accidental cell death due to acute injury
Non controlled event, causing rupturing of cells and leakage into surrounding tissues (inflammation)
Apoptosis & caspases
- Both pathways activate initiator caspases
How are cells killed quickly and neatly?
Initiator caspases cleave, and activate,
downstream executioner caspases, which
dismember numerous key proteins (e.g.
enzymes, structural proteins)
What is the process of cells dying?
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
- Cell signalling plays a role in maintaining the correct balance
Either excessive or insufficient apoptosis can contribute to disease
- Not enough apoptosis leads to the formation of tumours
- Too much apoptosis leads to cell loss and degeneration
Not enough Apoptosis - Contributes to tumours
- Cancerous cells have mutations allow them to block/escape apoptosis (cancer hallmark). As a result, they can survive longer and gives more time for the accumulation of mutations and be more malignant
Too much apoptosis
- Cell loss and degeneration
