Eukaryotic Cell Cycle and Cancer

This week we learned more about the eukaryotic cell cycle and how cancer forms. Because I wasn’t in class on Thursday when everyone did the cancer lab, I was instructed to write about the biointeractive cell cycle and cancer activity.

Big idea 3.A.2

The two types of cell division are mitosis and meiosis. Meiosis is a type of cell division that reduces the number of chromosomes in the parent cell by half and produces four gamete cells. This process is required to produce egg and sperm cells for sexual reproduction. Mitosis results in two daughter cells, each having the same number and kind of chromosomes as the parent nucleus. This usually occurs for tissue growth and to repair damages.

Every time the cell goes through mitosis cell division, it goes through four main stages; growth (G1), DNA replication (S), preparation to divide (G2), and finally, division (M).

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In each phase, there are events called checkpoints. Specialized proteins called “cell cycle regulators” or “checkpoint proteins” regulate the progression from one phase of the cell cycle to the next. Each checkpoint is strictly regulated and generally work without error. However, when an error does occur, it can create catastrophic events like the beginning of cancer.

In the G1 phase, a newly divided cell enters and increases in size, and also prepares for the replication of DNA. When the cell reaches the checkpoint, there are certain standards that must be met; the DNA must be healthy and there must be sufficient resources for the cell to continue to grow more and eventually divide. If it passes, the stimulating proteins, or CDC-cyclins, drive the cell into the S phase. If it does not, the cell either dies or moves into the G0 state.

In the S phase, the cell replicates its DNA. At the end of this phase, the cell has two complete sets of chromosomes. At the checkpoint, the DNA is checked for replication errors. If it passes, growth factors stimulate its movement to the G2 stage. If DNA damage or errors in DNA replication occur during the replication process, several proteins recognize these errors and trigger signals that stall the cell cycle until the problem is fixed. If it is far too damaged, the cell will die.

In the G2 phase, the cell continues to grow and prepare for division. At the checkpoint, the cell is checked again to make sure the DNA is not damaged, the full replication of chromosomes, and enough cell components are present. If there is DNA damage or incomplete replication, a number of inhibitory proteins prevent activation of the CDK-cyclin complex. Once the damage is fixed, the CDK-cyclin complex is activated and the cell can progress from G2 to M phase. If the damage is excessive and can’t be fixed, p53 can initiate apoptosis.

In the M phase, the cell stops growing and divides into two daughter cells, each with the same number of chromosomes.

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The M checkpoint checks to make sure that each chromosome in a pair (aka a sister chromatid) should be attached to the mitotic spindle. M-checkpoint inhibitory proteins include two mitotic arrest deficient (MAD) proteins. When chromosomes are not properly attached to the mitotic spindle, MAD proteins inhibit the anaphase-promoting complex/cyclosome (APC/C), preventing entry into anaphase. This prevents chromatids from being pulled apart into two daughter cells with an unequal number of chromosomes. during the cell division, M-phase cyclins and CDKs activate the APC/C complex. APC/C is activated when all chromosomes are attached to the mitotic spindle during metaphase—the stage in mitosis during which chromosomes are tightly packed and aligned near the middle of the cell. The active APC/C stimulates the destruction of proteins that hold the two copies of each chromosome together, allowing the chromatids to separate and move to opposite sides of the cell. The stage of mitosis when this separation occurs is called anaphase. And boom! A new cell is created.

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But what happens in the cell cycle that generates cancer cells? Cell cycle regulators are proteins that control the progression of a cell through the cell cycle and can either stimulate or inhibit cell cycle progression. Genes that encode these proteins are referred to as proto-oncogenes (stimulators) and tumor suppressor genes (inhibitors). Mutations in these genes can lead to cancer. These mutations lead to the uncontrolled division of cells, which can continue indefinitely.

A large contributor to the creation of cancer are mutations in the stimulator or inhibitor genes. When mutated, proto-oncogenes are turned into just oncogenes and “put their foot on the gas pedal,” or increase stimulation much more. When tumor supressor genes are mutated, it leads to a loss of inhibition, which “takes puts the foot off the brake,” allows the production to continue without stopping damaged or bad cells. Mutations in proto-oncogenes cause a gain of function and are dominant: a mutation in just one allele will produce a protein that puts the cell cycle into overdrive. Tumor suppressor gene mutations, which result in a loss of function, are recessive: both alleles have to be mutated for the cell cycle to be affected. Both of these mutations can lead to cancer cells.

Most of this is making sense to me, but I think it’d be super helpful to review more of the basic vocabulary, like chromatids vs chromosomes and all the other cell cycle components. It’s easy to forget which word means which.


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