The cell cycle Flashcards
What is the purpose of the cell cycle?
To replace all the cells in our organs and to ensure that all our cells are functional
How often do all (of most) of your cells get replaced?
Every 7 years
Can cells divide indefinitely?
No
How many cycles approximately can a cell undergo before dying?
~50
What kind of cell types don’t divide often? What do these particular cells have that makes them special?
Stem cells
Contain the master copy of the DNA
When do stem cells divide? What do they do between dividing?
Only when they have to
In a resting state
What does cell theory state?
That all organisms are made from cells and all cells come from preexisting cells
Cell theory states that all cells come from preexisting cells, what kind of cells are these?
Either stem cells or parent cells
What is the primary aim of the cell cycle?
Produce two daughter cells that are genetically and functionally identical to the parent cell
What is the cell cycle heavily regulated?
So that cells don’t appear at the wrong place at the wrong time
What is mitosis?
The process of DNA replication
What are the phases of mitosis?
Prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis
How is DNA packed before cell replication? Why is this?
Decondensed and mixed up
So that the transcription machinery can access the DNA
What are the 4 phases of the cell cycle?
G1 phase, S phase, G2 phase, mitotic phase
How long does each cycle last approximately?
G1 phase = 8-10 hrs
S phase = 8 hrs
G2 phase = 4-6 hrs
Mitosis = 1 hr
What is and what is happening in interphase?
The period between which cells are not dividing
It is when the cell is metabolically active and is producing and folding proteins
What are the phases involved in interphase?
G1, S, G2
What happens in the G1 phase?
Growth/Gap phase 1: Cell is metabolically active and is replicating all of its cellular organelles (e.g. mitochondria, ER…) and components except DNA and the nucleus, replication of the centrosomes begins
What happens in the S phase?
Synthesis phase: DNA strands are separated at the hydrogen bonds holding nucleotides tighter and new strand of DNA is synthesised
What happens in the G2 phase?
Growth/Gap phase 2: Cell ensure that DNA synthesis has completed and it has been done correctly, prepared for mitotic phase and replication of centrosomes
What is the purpose of the G1 phase?
To set the cell up for DNA replication
When do cells undergo the G1 phase?
If there are nutrients available, the tissue is healthy and if there is space to grow
Why would a cell not undergo the G1 phase?
If there isn’t space, if the cell is already touching other cells, if there aren’t sufficient nutrients
If a cell doesn’t undergo the G1 phase, what does this mean for the rest of the cell cycle? What will they be doing?
The cell won’t undergo the other cell cycle phases (e.g. won’t replicate)
The cell will continue to perform its cellular functions (e.g. producing proteins, detoxifying…)
Is the synthesis of DNA controlled? What does this result in?
It is highly controlled
Results in the DNA being copied error free
What happens in the mitotic phase?
Mitosis, where nuclear membrane is dismantled and the two copies of DNA are separated from each other and 2 nuclei are formed each containing one copy of DNA
What happens in prophase?
The DNA begins to condense and form chromatid pairs (pair up with the copied strand of the chromosome), mitotic spindle form a microtubule organising centre and go towards the nucleus
What happens in pro metaphase?
Nucleolus disappears and nuclear envelope breaks down, spindle fibres attach to sister chromatid at kinetochores (which are located on the centromeres which bind chromatids together) and the kinetochore microtubules (spindle fibre)
What is the kinetochore? What happens if spindle fibres can’t find kinetochore?
The attachment site for the spindle fibres on the centromere
Spindle fibres keep looking until they are found
What happens in metaphase?
Chromosomes line up along imaginary plane called metaphase plate,
Why do the chromosomes line up in metaphase?
To ensure they are in the right orientation and so that the tubule fibres are still attached to the spindles
What happens in anaphase?
The kinetochore microtubules disassemble so that the spindle fibres drag the sister chromatids to opposite ends of the cell
What happens in telophase?
Nuclear envelope re forms around each set of chromosomes, spindle fibres disintegrate and dispatch from the centromere
What happens in cytokinesis?
An actin and myosin ring causes the plasma membrane to pinch in and separate the cytoplasms and results in two new cells
What happens if something goes wrong during the mitotic phase?
The process will pause and the cell will determine if to go on
What happens if the process is unbalanced?
A different number of chromosomes end up in each cell
What is the name for a cell that has more or less chromosomes that what it should have? What does impact does this have on the cellular function?
Aneuploidy
2 chromosome = twice as much protein produced than what is required, Missing chromosome = no protein produced, both of these alter cellular function which can lead to cancers or somatic cell dysfunction
What normally happens if mitosis doesn’t occur correctly (e.g. causing aneuploidy or some other issue with the daughter cells)?
The cell will undergo apoptosis (programmed cell death)
How does cell cycle length vary between different cell types?
Cells that have a high turn over rate go through the G1 phase very quickly
Cells that are non-dividing stay in G1 permanently
What do cells with a high turn over rate require?
A large quantity of nutrients
What is the permanent state of G1 called in non-dividing cells?
G0
What kind of cells are non-dividing? What may causes them to divide? What would the parent cell be for these?
Neural cells
If they are stimulated by damage for example
Stem cells are the parent cells for neural cells
What kind of cells are rapidly dividing? What may causes them to divide?
Liver cells
If there is some kind of rapid change in the environment resulting in damage (e.g. toxins)
What are the three major checkpoints in the regulation of the cell cycle?
G1 to S checkpoint
G2 to mitotic phase
M checkpoint / SAC (spindle assembly checkpoint)
What do the cell checkpoints check for in the G1 to S phase? In what circumstances would the cell no continue with the cell cycle from this point?
If there are enough nutrients, the condition of the cell (social signals), if it is big enough and if the DNA is in good condition
If there cell doesn’t have enough nutrients, if it is in good working order the cell cycle is stopped, if the DNA is damaged
What gets checked at the G2 to M checkpoint?
If all the proteins for mitosis have been made, if there has been a mistake in DNA synthesis and activated MPF (mitosis promoting factor) is activated
What is the function of mitosis promoting factor?
To stimulate the cell into mitosis
What does the M checkpoint / SAC check?
Microtubules are still attached to kinetochores
What happens if the cell doesn’t get past the G1 to S checkpoint?
It stays in the G1 phase or goes into the G0 phase (where it will not progress further in the cell cycle)
What is MPF made of?
2 distinct polypeptide sub units: protein kinase and cyclin
What does protein kinase do? How does the concentration of this change throughout the cell cycle?
Phosphorylates the proteins driving them into bioactivity
Conc doesn’t change much
What regulates protein kinase from phosphorylation? How does the concentration change throughout the cell cycle?
Cyclin
Increases during interphase peaking in the M phase then rapidly decreasing
Is cyclin controlled during the cell cycle? Why?
Yes
It is necessary to stimulate the cell into mitosis at the correct time
When is the MPF protein kinase active?
Only when bound to the cyclin subunit
How does the concentration of cyclin impact activity of MPF? What does more MPF do?
Increasing conc of cyclin = increasing activity of kinase
Phosphorylates more proteins involved in the initiation of mitosis
What does phosphorylation generally do to a protein?
It makes it more bioactive
How do cyclins become biologically active?
They have to become de-phosphorylated (yes it is the opposite)
How does de-phosphorylation affect MPF functionality?
It makes them search out for their target proteins
What does MPF phosphorylate? What impacts on their functions does it have?
Histones, initiating the M phase
Lamina, initiates nuclear envelope breakdown
Microtubule associated proteins, activates mitotic spinal
Enzymes that degrade cyclin so that cyclin conc decreases (therefore switching cycle off)
If MPF is not regulated properly what happens to the cell?
It will either die or become a cancer cell
What are some of the functions that Mitosis-phase promoting factor (MPF) does?
- Activates protein to cause chromosome to condense (prophase)
- Catalyses degradation of MPF cyclin
- involved in mitotic spindle formation
- degradation of nuclear envelope
- Breaks down golgi matrix
How is MPF disassembled?
When anaphase-promoting complex (APC) polyubiquitinates (adds ubiquitin to molecule) cyclin
When is APC initiated/MPF disassembled?
During anaphase
How is the concentration of cyclin related to the concentration of anaphase-promoting complex (APC)?
As conc of cyclin increases, APC also increases
What is the function of a cell-cycle checkpoint? What does it prevent?
A critical point in the cell cycle ensuring that any errors in the interphase or mitotic phase processes do not get passed onto daughter cell
What happens if a daughter cell is made even when there have been errors in the cell cycle?
Tumors form
What is cancer?
Out of control cell division
What are all cancer derived from?
From cells in which cell cycle checkpoints have failed
What kinds of DNA changes are involved in cancer?
Genes that ordinarily promote growth/cell cycle activity: proto oncogenes (cells that are about to become cancerous but can undergo programmed termination) become oncogenes (cancerous)
Genes that stop or inhibit growth/stop cell cycle: tutor suppressor genes become inactive
What genetic changes happens to most people when they get cancers?
Switching on of genes that promote cell cycle activity and switching off of genes that stop the cell cycle at checkpoints if there are things wrong detected
What is proto-oncogene? How long does it last in the cell?
A gene that produces a protein that promotes progress through the cell cycle
It is normally expressed for a short specific time then degraded
What is oncogene? How long does it last in the cell?
Gene that reduces a protein that did promote progress through cell cycle but is now mutated and acting abnormally
May be expressed for short inappropriate times or remain in the cell for extended periods of time
What is a very common protein that becomes an oncogene?
RAS
What does RAS normally do when not an oncogene?
It is involved in a number of signalling phosphorylation cascades
What are the functions of the cascades that RAS is involved in?
Cell-cycle progression, transcription, cytoskeletal signals, translation, vesicle transport, calcium signalling (know 3 FYI)
What is a very common cascade that is affected by a oncogene RAS? What are the proteins involved in this?
Affects the RAF cascade
RAF –> MEK –> ERK –> PLA2, ELK1, RSK
What are the impacts from the the oncogene RAS on the RAF cascade? What are the impacts on the organism?
Causes the RAF cascade to be permanently switched on
This causes the cell-cycle progression and transcription to occur continuously
What are the changes on the DNA that lead to cancer? What is the affect of each change?
Mutation within the gene: hyperactive growth stimulation protein produced
Amplification of the gene (multiple copies): protein is produced in excess
Promoter is moved to new DNA position: protein produced in excess
People who are under the age of 50 typically get cancers how?
Inherited mutation on the DNA (FYI if you are a carrier for a genetic cancer, if the functional gene gets damaged then you get cancer, if you have 2 functional copies of the genes then you have a ‘back up’)
What is a tutor suppressor gene?
A gene that produces a protein which functions to halt cell cycle progression when appropriate so that cells checkpoints operate correctly
What is a mutated tutor suppressor gene?
Gene that produces a protein which function to allow progression through cell cycle inappropriately (e.g. doesn’t stop non-functioning components of cell-cycle progressing)
What does p53 do?
A regulator of the cell cycle ensuring the cell doesn’t go through the cell cycle if there is a problem detected in the checkpoints
How does functional p53 work?
Damaged DNA creates an intracellular signal that is sensed by protein kinases with then activates p53. Activated p53 promotes the production of a protein that inhibits the cell cycle at that point, if DNA is unrepairable signals for apoptosis
How does non - functional p53 work? How does it cause cancers?
Damaged DNA creates an intracellular signal that is sensed by protein kinases with then activates the dysfunctional p53. p53 is unable to initiate transcription for the protein needed to inhibit the cell cycle so any damage gets passed on through cell cycle.
The cells produced by this are non-functional and over divide causing cancerous growth
What is the pathway of COLON cancer from healthy tissue to cancerous tissue?
1 - loss of tutor suppressor gene such as APC, this causes a small growth (polyp –> these names are specific for epithelial tissue FYI) - not cancerous
2 - RAS oncogene is activated and tumour suppressor gene DCC is deactivated causing a larger growth (adenoma) - not cancerous as it is not growing out of control
3 - tumor suppressor p53 and further mutations on DNA result in a cancerous tissue forming (carcinoma)
How many new colon caner diagnosis are made in AUS and NZ every year?
13,000
What is the difference between a tumour and cancer? Are all cancers tumours and are all tumours cancers?
A tumour is a lesion/bump formed by abnormal cellular growth, cancer is when this is uncontrolled growth
All cancers are tumours (cancer = out of control tumour) but not all tumours are cancers (some tumour are benign)
How can a cancer spread to other parts of the body?
The tumour will infiltrate the lymphatic system and colonise the lymph nodes
