WEEK 10 (Cell division) Flashcards
What is the function of the cell cycle?
- Duplicate the vast amount of DNA in the chromosomes
- Segregate the DNA into genetically identical daughter cells so each cell receives a complete copy of the entire genome
Why do cells duplicate its other macromolecules and organelles and doubles in size before it divides?
Otherwise each time a cell splits it would get smaller and smaller
What are the four stages of the cell cycle?
- G1 PHASE
- S PHASE
- G2 PHASE
- M PHASE
Which phases are in Interphase?
- G1PHASE (Increases in size)
- S PHASE (DNA Replication)
- G2 PHASE (Prepares to divide)
[At particular points in G1 and G2, the cell decides whether to proceed to the next phase or pause to allow more time to prepare]
What is the importance of Interphase?
- Cell continues to transcribe genes, synthesise proteins and grow in mass
- Provide time needed for the cell to grow and duplicate its cytoplasmic organelles
What is the G zero phase/Resting phase?
A period in the cell cycle in which cells exist in a quiescent state
What is the difference between Liver cells and Nerve & muscle cells in a quiescent state?
Liver cells in the G zero phase = can be “called back” to cell cycle by external cues
Nerve & muscle cells in the G zero phase = arrested in that phase and can never divide
When are cells during the cell cycle put in the ‘Resting phase’?
- Enough cells
- Mutation in the cell that needs to be fixed before differentiation
- Cell during its division gets damaged
What is the function of checkpoints in the cell-cycle?
Ensures that key processes in the cycle occur in the proper sequence
What are the three checkpoints in the cell cycle?
- G1 CHECKPOINT = determines whether the cell proceeds to the S phase
- G2 CHECKPOINT = determines whether the cell proceeds to mitosis
- M CHECKPOINT = determines whether the cell is ready to pull the duplicated chromosomes apart and segregate them into two new daughter cells
How do cells know when to divide?
Cell communication signals (Activators & Inhibitors)
What is the function of Cyclin-dependent Kinases (CDKs)?
- Phosphorylates cellular proteins
- Activates or inactivates proteins
What is the function of the CDK-Cyclin complex?
Triggers passage through different stages of cell cycle
What are Cyclins?
Proteins that regulate cell division and control the progression of cells through the cell cycle by activating cyclin dependent kinases enzymes
When is Cyclin-B made?
In G2 phase and M-phases of the cell cycle and combines with CDK1 to form the M-phase Promoting Factor (MPF)
Describe how Timothy Hunt discovered cyclins
By studying the fertilisation of sea urchin eggs he found that one protein had disappeared at the end of cell division and appeared again at the next round of division -> Concluded that “CYCLIN” protein was driving the cell cycle
What is the function of The cell-cycle control system?
The cell-cycle control system governs the CELL-CYCLE MACHINERY by cyclically activating and then inactivating the key proteins and protein complexes that INITIATE and REGULATE DNA replication, mitosis and cytokineses through PHOSPHORYLATION (PROTEIN KINASES) and DEPHOSPHORYLATION (PROTEIN PHOSPHATASES)
_________________ are present in proliferating cells throughout the cell cycle but are activated only at appropriate times in the cell cycle
Protein Kinases
[Although enzymatic activity of the cyclin-cdk complex rises and falls during the course of the cell cycle, the concentration of the CDK DOES NOT but concentration of CYCLINS DOES]
Describe the mechanism of Cyclin
- Cyclin-dependent kinase (Cdk) must bind CYCLIN before it can become enzymatically active
- Active cyclin-Cdk complex PHOSPHORYLATES key proteins in the cell that are required to initiate cell cycle
- CYCLIN helps direct the Cdk to the target proteins
Cyclins have no enzymatic activity themselves (TRUE/FALSE)
TRUE
What does an increase in the cyclin concentration do?
It helps form the active cyclin-Cdk complex that drives entry into M phase
What do different cyclin-Cdk complexes trigger?
Different steps in the cell cycle
What are the two types of regulation of CDKS activity?
- NEGATIVE REGULATION
- POSITIVE REGULATION
How does Negative regulation of Cdks activity work?
- By destruction of cyclin
- Ubiquitylation
[the process of attaching ubiquitin, a small protein found in almost all tissues of eukaryotic organisms, to another targeted protein] - By inhibition
How does Positive regulation of Cdks activity work?
Cdc25-protein phosphatase
What does the abrupt degradation of M and S cyclin part way through the M phase depend on?
Anaphase-promoting complex (APC)
How does the Anaphase-promoting complex (APC) work?
The Anaphase-promoting complex tags the S or M cyclin with UBIQUITIN (UBIQUITYLATION) which marks the protein for destruction in proteasomes -> The loss of cyclin makes the Cdk partner inactive -> Cyclin destruction helps the transition from one phase of the cycle to the next e.g out of mitosis
Apart from phosphorylation and dephospho rylation, how can the activity of Cdks also be modulated?
By the binding of Cdk inhibitor proteins
What must happen to the Cdk to make it active?
It must be phosphorylated at one site and dephosphorylated at two other sites
Describe how Cdks become active
When it first forms, the CYCLIN-CDK COMPLEX is not phosphorylated and is inactive -> Cdk is phosphorylated at a site that is required for its activity and at two other sires that inhibit its activity -> Phosphorylated complex remains INACTIVE until it is finally activated by a PROTEIN PHOSPHATASE that removes TWO INHIBITORY PHOSPHATE GROUPS
What are the ways the cell cycle control system can pause the cycle?
- CDK INHIBITORS = block entry to S phase
- INHIBITING ACTIVATING PHOSPHATASE = blocks entry to mitosis
- INHIBITION OF APC ACTIVATION = delays exit from mitosis
What is the function of Mitogens?
Mitogens promote the production of the cyclins that stimulate cell division
Describe how Mitogens function
Mitogens act by switching on cell signalling pathways that stimulate the synthesis of G1 cyclins, G1/S cyclins and other proteins involved in DNA synthesis and chromosome duplication
What is the Retinoblastoma protein?
- Negative control of Mitogens
- Abundant in the nuclei of all vertebrate cells
- Binds to particular transcription regulators and prevents them from turning on the genes required for cell proliferation
Describe Retinoblastoma
Retinoblastoma is a rare malignant tumour of the retina in infants. 40% is HERITABLE where the child inherits a mutant allele at the RETINOBLASTOMA LOCUS (RB1). 60% is SPORADIC where RB1 alleles in a single retinal cell have been inactivated independently (occurs in one eye only).
CAUSES: A randome mutation of RB locus in retinal cell completely removes inhibition of Rb protein -> affected cell grows into a tumour
SYMPTOMS:
- Vision problems
- Eye pain
- Redness of the white part of eye
- A pupil that doesn’t get smaller when exposed to bright light
- Bleeding in the front part of the eye
- A different colour in each iris
SYMPTOMS THAT INDICATE NON-HEREDITARY RETINOBLASTOMA:
- One eye drifting towards centre
- Decreased viision
- Inflammation
- Glaucoma
- Pain in eye
- Redness in eye
What happens when DNA in G1 is damaged?
- The cell cycle stops to give the cell time to repair the damaged DNA before replicating it
- If DNA damage is too severe -> p53 can induce the cell to undergo APOPTOSIS
What happens when DNA is damaged or incompletely replicated in the M phase?
Cdc25 is inhibited preventing the removal of INHIBITORY PHOSPHATASES -> M-Cdk remains inactive and M phase is delayed until DNA replication is complete and any DNA damage is repaired
How does M-cdk drive entry into the M phase and mitosis?
Activated M-Cdk indirectly activates more M-Cdk creating a POSITIVE FEEDBACK LOPP -> Once activated, M-Cdk phosphorylates and activates more Cdk-activating phosphatase -> Phosphatase activates more M-Cdk by removing the inhibitory phosphate groups from the Cdk subunit
What are the two multiprotein complexes that help to form and organise metaphase chromosomes?
- CONDENSINS = help coil each sister chromatid into a smaller, more compact structure that can be more easily segregated during mitosis
- COHESINS = tie together the two adjacent sister chromatids in each duplicated chromosome
Describe the alignment of sister chromatids via cohesin
1) At the end of S phase -> uncondesnsed sister chromatids and arms are together
2) At the beginning of Prophase -> condensed sister chromatids and arms are together
3) In the middle of Prophase -> cohesions along chromosome arms are released, condensed sister chromatids and arms are free
4) At Anaphase -> condensed chromatids have separated and cohesin at centromere is degraded
Describe how the cohesion linkage is destroyed
Before anaphase begins, protease is held in an INACTIVE STATE by SECURIN -> At the beginning of anaphase, SECURIN is targeted for destruction by APC (APC triggers the separation of sister chromatids by promoting the destruction of COHESINS) -> Once SECURIN is removed, SEPARASE is free to sever the cohesion linkages
The cohesion linkage is destroyed by a protease called ________________
Separase
What are the two cytoskeletal structures that mediate M phase in animal cells?
- MITOTIC SPINDLE (microtubule) = assembles first to separate the replicated chromosomes
- CONTRACTILE RING (actin and myosin) = assembles to divide the cell in two
What happens in Prophase?
- Duplicated chromosomes condense
- Outside the nucleus, mitotic spindle assembles between the two centrosomes
What happens in Prometaphase?
- Abrupt breakdown of nuclear envelope
- Chromosomes attach to spindle microtubules via kinetochores and undergo active movement
What happens in Metaphase?
- Chromosomes align in the middle
- Kinetochore microtubules on each sister chromatid attach to opposite poles of the spindle
What happens in Anaphase?
- Chromatids separate to opposite poles
- Kinetochore microtubules get shorter
- Spindle poles move apart
What happens in Telophase?
- Two sets of chromosomes arrive at the poles of the spindle
- New nuclear envelope reassembles around each set
What happens in Cytokinesis?
Cytoplasm is divided in two by a contractile ring of actin and myosin filaments which pinches the cell into two daughters, each with one nucleus
