Case 4- cell cycle Flashcards
What is the cell cycle
The time between two cell divisions
Cell cycle- G1
Growth stage, increase in size
Cell cycle- G0
Resting stage, dormant stage which cells enter to exit the cell cycle. If they want to re-enter the cell cycle they enter at G1
Cell cycle- S
DNA is replicated to produce another copy. Takes about 12 hours. All genetic material is replicated. The two sister chromatids are held together by a centromere
Cell cycle- G2
Another growth stage, increase in size and prepares for mitosis. Can vary in length depending on cell type
Cell cycle- M
Division of cell to produce two new cells. Involves mitosis and cytokinesis. In mitosis the chromosomes are separated between the two new cells and in cytokinesis the cytoplasm splits to produce two new cells. Nuclear envelope and cell mebrane are reformed
Sequence of mitosis
Prophase, metaphase, anaphase, Telophase
Prophase
The chromosomes condense to become more compact, so they are easier to separate, in late prophase the mitotic spindle is formed
Metaphase
In protometaphase the chromosomes organise themselves within the cell, chromosomes attach to spindle. The nuclear membrane breaks down. In metaphase the chromosomes line up along the equator of the cell.
Anaphase
The chromosomes are pulled apart so one full copy of the chromosome move to each pole of the cell, this is done by the mitotic spindle
Telophase
The nuclear membrane begins to reform around each set of chromosomes
The checkpoints in the cell cycle
1) The restriction point between G1 and S
2) The S-phase checkpoint
3) The checkpoint between G2 and M
4) The checkpoint in the metaphase to Anaphase transition
Checkpoints in the cell cycle- The restriction point between G1 and S
Is the environment favourable, is there a growth stimulatory pathway. Is there enough growth stimulation for the cell to divide? Is the DNA good for replication?
Checkpoints in the cell cycle- The S-phase checkpoint
Checks that DNA synthesis has happened correctly, there should be a full complete copy.
Checkpoints in the cell cycle-The checkpoint between G2 and M
Checks that the DNA has replicated correctly and that the environment is favourable. Is there still a growth stimulatory signal?
Checkpoints in the cell cycle- the checkpoint in the Metaphase to Anaphase transition
Checks that the chromosomes can correctly separate to each end of the cell. Anaphase bridges can occur where the chromosomes remain attached together, eventually this will snap but it may not allow for one full set of chromosomes to go to each end of the cell. May snap unevenly which will affect cell division which could lead to cancer. Has the mitotic spindle correctly attached to the chromosomes and are the chromosomes aligned?
What happens if an error is detected at a checkpoint?
The cell cycle can be blocked to stop the errors from being passed to other cell to avoid uncontrolled cell division
How does the cell control movement through the checkpoints
Through enzymes, specifically cyclin dependent kinases (Cdks). Cyclin-Cdk complexes trigger events in the cell cycle by phosphorylating specific target proteins. This drives the cell through the checkpoints.
Enzymes in G1
Cyclin D binds to CDK4 and CDK6 which push the cell through its cycle.
Enzymes at the end of G1
Cyclin E activates CDK2 to drive it through the checkpoint.
Enzymes at the end of S phase
Cyclin A activates CDK2 to get to the G2 stage.
Enzymes in G2
Cyclin A binds to CDK1.
Enzymes at the end of G2
Cyclin B binds/activates CDK1 to get through that checkpoint and for mitosis to occur. So, the right cyclin needs to be present at the right point.
To stimulate the cell cycle
1) A mitogen (growth factor) binds to a receptor.
2) Once the receptor has been activated the signal is sent down the cell by activating Ras GTPase (transducer).
3) This induces a signalling cascade which activates MAP kinase.
4) The signal arrives at the nucleus and there is an increase in Myc transcription (transcription factor). This transcription factor cause transcription of the G1 cyclins, the increase in cyclins causes the CDKs to be activated.
5) The cell then progresses through the cell cycle. Many genes in this pathway are linked to cancer (oncogenes).
To inhibit the cell cycle
When something has gone wrong. There are a series of proteins that inhibit the cyclin-CDK complex. The inhibitors are the INK4 family and the Cip/Kip family.
Cell cycle- P53
An important gene in the suppression of the cell cycle and stops it dividing in an uncontrolled way, is a tumour suppressor. It indirectly inactivates G1/s-Cdks and S-Cdks. In also plays a role in programmed cell death (apoptosis). It activates p21 which inhibits the cell cycle to check what the mistake is and if repair is possible, if it cannot be repaired apoptosis occurs. A mutation on this gene is common in cancer, results in half of all cancers. It’s a target for viral oncoproteins which can cause cancer by inhibiting its activity. Target of many anti-cancer drugs. P53 will be active due to excess mitogenic pressure, errors in mitosis, DNA damage, oncogene activation and cell stress.
How mistakes in telomeres can lead to cancer
The telomere gets shorter after each cell division. If the cell continues to divide after the telomere becomes very short, then vital genes will be lost. In some cancer cells they divide when the telomere is too short, they divide indefinitely, and genes get lost.
How mistakes in KRas can lead to cancer
You lose cell cycle control in cancer by overactivation of the genes that stimulate cell division. E.g. KRas which activates the RAS/MAPK pathway, KRas is an oncogene. Another way to lose control is through inactivation of the gene that inhibits cell division i.e. p53 which is a tumour suppressor gene. Cancer cells will have multiple mutations
What causes cancer
If the cell cycle goes wrong you will get cells that divide more rapidly then normal and this can lead to tumour formation. Cancer is driven by genetic alterations (mutations in DNA or epigenetic changes). These alterations can be due to a DNA damaging stimulant or a spontaneous DNA replication error. This cell will collect mutations as it divides till it has enough mutations to divide in a completely uncontrolled way. A cellular mass forms which develop into a tumour. The cancer cell can no longer perform its function
How do cancer cells affect adjacent cells
They interfere with adjacent cellular function at the originating site by creating a necrotic environment. Can also be when the tumour compresses neighbouring organs or structures. They can also completely colonise that area of the body, meaning more of the organ loses function.
What features do cancer cells have
Abnormal cellular morphology, increased rate of mitosis, multi-nucleated cells, increased nuclear DNA and disorganised tissue architecture.
Oncogene
Genes involved in cell division e.g B-raf kinase
Tumour suppressor gene
Genes involved in preventing cell division
Cancer- transformation
The process by which a cell becomes cancerous
Cancer- clonality
Being genetically identical
Carcinogen
A substance which promotes genetic mutations and cancer formation
Cellular oncogene
When structures within the cell cause mutations
Viral oncogene
When a virus causes a mutation
Proto- oncogene
The original form of a cell before it becomes cancerous
