Cell Cycle: Interphase and Mitosis

Phases

The cell cycle is divided into five distinct phases gap 0 (G₀), gap 1 (G₁), synthesis (S), gap 2 (G₂), and mitosis/meiosis (M). These phases can be further grouped into non-replicative and replicative phases where G₀ is non-replicative and G₁, S, G2, and M are all part of the replicative phase. Additionally, the cell cycle can be split into interphase which encompasses G₀, G₁, S, and G₂ and serves to prepare the cells for division and M phase in which cells undergo active division.

Interphase

G₀: Resting Cells

Cells that aren’t undergoing active replication or preparing to do so exist in the G₀ phase. Here cells are carrying out their basic day to day functions. Many terminally differentiated cells or slow/non-replicative cells such as neurons, muscle cells, and hepatic cells exist in this stage. While neurons and muscle cells are essentially stuck in G₀ forever hepatic cells found in the liver can switch back into G₁ and replicate when damaged.

This ability to switch leads to very different consequences when the different tissues are damaged. For example, strokes in which brain tissue is damaged lead to long-term deficits in motor, speech, or autonomic functions depending on the area of the brain affected. In contrast, a living donor can give up to two-thirds of their liver away since hepatic cells can switch out of the G₀ phase and regrow the missing tissue via the cell cycle, unlike our neurons which are unable to replicate.

G₁: Prepare For Synthesis

Once a cell has decided to replicate it needs to get ready to do so and make sure no DNA damage or mutations have occurred in the cell’s DNA. If a mutation or DNA damage is detected the cell will either undergo apoptosis or attempt to fix the damage present. Either way, G1 serves as a restriction point that prevents cellular errors from accumulating in newly created cells.

Additionally, the cell needs to prepare for splitting into two and will generate extra organelles, increase its cell membrane size, and increase its cytoplasmic volume.

S: Synthesize New DNA

DNA acts as an instruction kit telling cells what to do and when. Therefore it is extremely important that the new cell gets a complete set of DNA from its older version.

In order for this to occur the cell replicates its DNA creating a new set of identical DNA strands in the S phase. These new strands are organized into chromosomes that consist of identical sister chromatids connected by a centromere. At this stage, the cell has 92 chromatids double the normal amount but only 46 unique chromosomes since the DNA was simply copied.

G₂: Synthesis Quality Control

Since replication is an error-prone process the cell will need to double-check its DNA again in the G₂ phase to make sure no mutations occurred during synthesis. If the DNA has been properly synthesized and the proper amount of organelles are present the cell gets the green light to enter the M phase and undergo division.

Cancer: The Cell Cycle Gone Awry

Despite a cell’s best efforts to check and double-check its DNA in interphase, mistakes happen. When this occurs mutated or damaged cells may end up dividing, producing more damaged or mutated cells as a consequence. Sometimes these mutations occur in the genes that control the cell cycle itself and result in uncontrolled cellular division which we call cancer.

Cancerous cells no longer stop at restriction points and as time goes on cancerous cells accumulate more and more errors as they bypass normal DNA repair checkpoints. Mutations in two different types of genes, proto-oncogenes and tumor suppressor genes, are responsible for the shift from a healthy cell to a cancerous one.

Under normal circumstances, both genes help keep the cell cycle in check using two distinct mechanisms. Tumor suppressor genes are like the brakes in a car allowing the cell cycle to slow down or stop. When mutations occur in these tumor suppressor genes the brakes malfunction and are no longer able to stop our out of control cell cycle. 

Proto-oncogenes on the other hand act as the gas pedal in our car allowing it to move forward and progress through different stages of the cell cycle. When mutated they transform into oncogenes which act like a stuck gas pedal constantly accelerating the cell through the cell cycle and rapid replication despite the presence of errors.

While mutations in either gene are deleterious it takes a combination of multiple mutations in a variety of proto-oncogenes and tumor suppressor genes for cancer to occur.

M Phase

Once a cell has made it past all of the necessary checkpoints it enters the M phase. Depending on the cell type the M phase can represent either mitosis or meiosis. Mitosis occurs in somatic cells or our non-reproductive cells such as those found in your liver, heart, and bone. Whereas meiosis occurs in germ cells or our reproductive cells and leads to the formation of gametes such as sperm and oocytes.

Ploidy

Before jumping into the two processes we need to first understand ploidy or how many copies of each chromosome a cell has. While different organisms have a variety of normal ploidies we will focus on human cells which under normal circumstances have two copies of each chromosome and are said to be diploid abbreviated 2n.

Mitosis starts with a 2n cell and will reproduce itself generating a genetically identical 2n cell at the end of the mitosis. Meiosis like mitosis starts with a 2n cell but generates a monoploid cell (n) with only one copy of the organism’s genetic material. Later during sexual reproduction, two n cells will combine to form a 2n cell with genetic material that is a mix of both of the n cells.

Mitosis or Cell Division

We will begin with mitosis since it is the simpler of the two processes and divided into different steps that are nearly identical to those seen in meiosis.

Prophase: Prep Step

The first step of mitosis called prophase begins the process of division by condensing cellular DNA into chromosomes. This step ensures that each cell gets an equal amount of DNA when the two split off from one another. Additionally, microtubules within centrioles begin to migrate to the opposite sides of the cell forming the centrosome. The positioning of the centrosome prepares the cell for later steps in which the two chromatids will be pulled apart. Once positioned the nuclear envelope dissolves and one end of the centriole attaches to the centromere via kinetochore that allows for microtubules to firmly attach themselves to the chromosome.

Metaphase: Meet in the Middle

Now that the cell is prepped the chromosomes migrate to the center of the cell in a stage called metaphase. At this point in time, all of the cell’s chromosomes are positioned directly in between both ends of the centrosome on the metaphase plate.

Anaphase: Apart We Go

At this point the cell enters anaphase and the centrioles attached to the kinetochore pull sister chromatids apart and to either side of the cell by shortening.

Telophase: Tear in Two

Finally, the cell is ready to be split into two in a stage called telophase. In this stage, the nuclear membranes of each cell reform and the DNA uncoils. Then the organelles are split into the two halves of the cell and cytokinesis occurs. During cytokinesis, the two sides of the cell are separated by actin fibers that constrict the central portion of the cellular membrane effectively cutting the cell into two by pinching the membrane shut. This leaves two genetically identical cells ready to carry out their intended functions.

Mnemonic: Pro MeAT

It can be a bit tricky to remember the order of the different steps in mitosis I like to use the mnemonic Pro MeAT to remember the order: Prophase → Metaphase → Anaphase → Telophase. To help cement this mnemonic and tie it to the cell cycle I think of a t-bone steak shaped cell picketing for a pro meat campaign. You know, “Beets it’s what’s for dinner!”

Meiosis

As discussed before, meiosis is the M phase for a sexually reproducing cell that results in the generation of gametes or n cells. While the steps seen in meiosis are the same as those in mitosis germ cells undergo two rounds of each step that results in the separation of sister chromatids. Since we have already seen all of the steps and now know what they do we will go through meiosis here quickly and will revisit this process multiple times when discussing gametogenesis and genetics later.

Meiosis I

Meiosis is separated into two rounds of the same steps. The difference is that DNA replication takes place prior to meiosis I but not prior to meiosis II. As a result of this the first set of cells created by meiosis I are diploid while the second set of cells created after the conclusion of meiosis II.

Prophase I

As in mitosis the chromosomes condense and go from their spaghetti to their chromosome form. When this occurs homologous chromosomes intertwine with one another and form a tetrad. Special proteins will hook the two chromosomes together and form the synaptonemal complex.

At this point sections along the arms of the homologous chromosomes will come into contact with one another forming chiasma. These chiasma exchange genetic information and shuffle up the alleles found on each strand. This is why an organism with an AaBb genotype will go onto produce AB, Ab, aB, and ab gametes.

Furthermore, chiasmata are decently large encompassing more than one gene at a time. This means that two genes that are right next to one another will often get swapped together. When this occurs the genes are said to be linked. So if the same organism above had a linked A-B and a linked a-b they would produce gamete with AB and ab genotypes instead of the full shuffling seen above. The closer together two genes are the higher the chance of them being linked.

The whole process of allele shuffling is called crossing over and it can happen multiple times. If it happens once it is called a single crossover when it happens twice it is called a double crossover. Crossing over allows parents to create genetically diverse offspring with a unique combination of genes. This variety increases the chances that offspring will have the “right” genes for the ecological niche they fill.

Metaphase I

Metaphase is a bit different too. Instead of lining up an individual chromosome to be ripped apart two homologous chromosomes are lined up on the metaphase plate.

Anaphase I

At this point, homologous chromosomes are pulled to either side of the cell. This overall process is called disjunction and separates the homologous chromosomes randomly. For example, a cell might receive chromosome 13 from the paternal side and chromosome 14 from the maternal side.

Telophase I

Lastly the two cells are split into two new daughter cells and the cells take a quick break called interkinesis.

Meiosis II

Following interkinesis meiosis II starts up, which is identical to mitosis except a monoploid cell is generated instead of a diploid one.