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Cell Cycle

If you've ever spent time around toddlers, the following scene should be familiar. The toddler is excited! They are taking some of their very first steps, and maybe they're moving a little too fast. OUCH!  They stumble and fall, scraping their knee on the ground. 

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Cell Cycle

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If you've ever spent time around toddlers, the following scene should be familiar. The toddler is excited! They are taking some of their very first steps, and maybe they're moving a little too fast. OUCH! They stumble and fall, scraping their knee on the ground.

To the toddler, this might be one of their very first injuries, and it's a big deal! Perhaps the skin on their knees is gone forever! It's hard to explain to a child that their leg will heal when they're feeling pain, but let's zoom in on this moment.

The skin cells from their knees really are gone for now, but not forever. How is it that this skin returns? The skin cells left over have a lot of work to do. These cells will have to produce clones, copies of themselves in a process called the cell cycle and cell division.

  • First, we will look at the diagram and phases of the cell cycle.
  • Then, we will talk about the regulation of the cell cycle.

Cell Cycle Diagram

The cell cycle describes the life cycle of a eukaryotic cell as it performs its necessary functions and prepares for cell division, producing two new daughter cells. The cell cycle is split into two phases: the interphase and the mitotic phase. Figure 1 shows the diagram of the cell cycle.

Cell Cycle interphase and mitotic phase wikipedia.org

Figure 1: The cell cycle: Interphase and the Mitotic phase, as well as the sub-phases: G1, S, G2, Mitosis, and Cytokinesis. Source: Wikipedia.org

Cell cycle phases

The cell cycle phases, interphase and the mitotic phase, are further broken down into sub-phases: G1, S phase, and so on. Let's explore each of these phases and sub-phase of the cell cycle more thoroughly:

Interphase

Interphase is the longest portion of the cell cycle, where the cell performs its essential functions and prepares for division. Interphase is broken down into three sub-phases: first gap phase (G1), synthesis phase (S phase), and second gap phase (G2). These cell cycle phases are described briefly below:

First gap phase (G1)

  • The cell performs all of its necessary functions.

  • Accumulates energy and proteins in preparation for the synthesis phase.

  • The cell grows so that it is large enough to be divided in two.

  • The first cell checkpoint ensures the cell is ready to move on to S phase.

Synthesis phase (S phase)

  • The cell undergoes DNA Replication, copying exactly all of the DNA chromosomes.

  • The chromosomes now form the recognizable X-shape, each half of the X being a full copy of the other side. Each half is called a sister chromatid.

  • Organelles called centrosomes are duplicated.

Second gap phase (G2)

  • The cell continues to grow and accumulate energy for the mitotic phase.

  • The organelles are duplicated for each daughter cell.

  • The cytoskeleton is dismantled into microtubules to be used during mitosis.

  • A second cell checkpoint ensures the cell is ready to enter the mitotic phase.

Mitotic phase

The mitotic phase of the cell cycle is when the cell separates its DNA chromosomes and cell components, leading to cell division and daughter cells. The mitotic phase consists of two sub-phases that occur simultaneously: mitosis and cytokinesis. Mitosis is the division of the DNA chromosomes and takes place over five sub-phases: prophase, prometaphase, metaphase, anaphase, and telophase. The deep dive below gives a brief overview of the sub-phases of mitosis. Cytokinesis is when cell division actually happens, producing daughter cells. In animal cells, an actin ring pinches the cell's plasma membrane together until it has split into two cells, almost like pinching a piece of clay into two. Plant cells, however, build a cell plate inside itself until it fuses with its outer cell wall and separates the two new daughter cells. With cytokinesis complete, the cell cycle is also complete and may begin once again for each of the daughter cells.

Prophase

  • In the first stage of mitosis, the chromosomes begin to condense and become visible.
  • Centrosomes separate to opposite sides producing spindle microtubules. These microtubules move the chromosomes in the cell, like puppet strings.
  • The nuclear envelope breaks down and moves to the edge of the cell, making way for mitosis.

Prometaphase

  • The chromosomes fully condense but are still being directed to the middle of the cell.
  • Spindle microtubules attach to each sister chromatid at structures called kinetochores.
  • The centrosomes have moved to opposite poles of the cell.

Metaphase

  • The chromosomes are aligned in the center of the cell on a straight line called the metaphase plate.
  • A cell checkpoint ensures that the spindle microtubules have attached to each sister chromatid's kinetochore correctly, in preparation to separate the chromosomes.

Anaphase

  • The mitotic spindles shorten, pulling each of the sister chromatids apart. Now that the chromatids have separated, they are called daughter chromosomes. Two full sets of DNA chromosomes should now be on opposite sides of the cell.
  • Unattached spindle microtubules elongate the cell into an oval shape, preparing it for cell division during cytokinesis.

Telophase

  • Two new nuclear envelopes form around the DNA chromosomes.
  • The chromosomes loosen into usable chromatin.
  • the spindle microtubules break down and are recycled into the cytoskeleton for the new daughter cells after cytokinesis.

Gap 0

Immediately after the mitosis cell division, the new cell may enter a quiescent stage called gap zero (G0) of the cell cycle, and will not continue to actively divide. This may be a temporary stage while the organism is under stress, before the cell moves into the G1 after some outside stimulus. Or it can be permanent in the case of nerve or heart cells that do not actively divide once fully formed.

Cell cycle regulation

Imagine, for a moment, that the cell did not have all the energy or proteins necessary to complete DNA replication. Maybe some of the chromosomes were completely copied, others only partly copied, and some not at all. How would this affect mitosis or the daughter cells that divide from this parent cell?

It could be disastrous! The daughter cells might immediately die, or live but be unable to complete their function, or continue dividing without stop causing cancer. To prevent this the cell tightly regulates the cell cycle using "checkpoints" between G1 and S phase, G2 and mitotic phase, and during metaphase of mitosis.

G1/S checkpoint

Moving into the S phase of the cell cycle is the point of no return for cell division, often called the restriction point. Once the chromosomes start to replicate the cell is committed to becoming two new cells. This first checkpoint in the cell cycle monitors if the cell is ready to complete DNA replication using extracellular signals, such as growth factors. The cell also checks its chromosomes for DNA damage. If damage is detected, it will pause the cell cycle. The cell may then try to repair the DNA if it can or move into G0 until it is ready or triggered to move into the S phase by another signal.

G2/ Mitotic phase checkpoint

This checkpoint looks to ensure that the cell is large enough and has enough energy to complete the cell cycle with mitosis and cytokinesis. But the main regulation that occurs here inspects the cell's DNA. If the chromosomes are not duplicated, or if they are damaged in some way, the cell stops the cell cycle and tries to fully replicate or repair the chromosomes, before continuing onto mitosis.

Mitosis metaphase checkpoint

This checkpoint happens during mitosis after the chromosomes are aligned on the metaphase plate, right before anaphase separates the chromosomes into what will become the daughter cells. This checkpoint ensures that the spindle microtubules have attached to the duplicated chromosomes correctly at the kinetochores. If microtubules are not attached correctly, the daughter cells may end up with too much or too little DNA, and the cell will halt mitosis until the spindle fibers are attached correctly. If everything gets fixed, the cell cycle will continue, finishing mitosis and cytokinesis.

Cell cycle regulator molecules

While the checkpoints take stock of the cell at certain, predetermined points, there are also intracellular molecules that help to push the cell along the cell cycle, or stop the cell cycle if they "notice" something is wrong. Molecules that help to continue the cell cycle engage in positive regulation, while molecules that may stop the cell cycle engage in negative regulation.

Positive regulation of the cell cycle

The key proteins that help to advance the cell cycle are called cyclins and cyclin-dependent kinases (Cdks). There are four cyclins that change in concentration to help to regulate the cell cycle (Fig. 2). As their concentrations increase in the cell, triggered by internal and external signals, the cyclins help to move the cell cycle into the next phase. After the cyclin initiates the next phase, they are quickly degraded.

Cell Cycle positive regulators wikipedia.com

Figure 2: The concentration of cyclin molecules during the cell cycle. Source:

wikipedia.org

Cyclins cannot act on their own and must bind to a Cdk. After the cyclin has bonded with a Cdk, it must also be phosphorylated by another kinase, to activate the cyclin/Cdk complex. Each phosphorylated cyclin/Cdk complex has a specific shape to bind and phosphorylate the next protein in the cell cycle regulation (Fig. 3). While the amount of cyclin fluctuates a lot during the cell cycle, the amount of cyclin-dependent kinases stay relatively constant but inactive until their specific cyclin protein is present to continue the cell cycle.

Cell Cycle Cyclin Dependent kinases openstax.org

Figure 3: Cyclin and cyclin-dependent kinases bind and are activated via phosphorylation from another kinase. The activated cyclin/cdk complex can now activate its target protein and advance the cell cycle. Source: openstax.org

Negative regulation of the cell cycle

The main negative regulatory molecules for the cell cycle include retinoblastoma protein (Rb), p53, and p21. These proteins are called tumor-suppressors because they were discovered while investigating cancer cells, when the cell cycle continues indefinitely, ignoring the cell cycle checkpoints. Rb, p53, and p21 work primarily at the restriction point: the G1/S phase checkpoint.

P53 is a main regulator in moving into S phase because it looks for and manages damaged DNA during G1 preparation. If p53 finds any damaged DNA, it will increase in concentration, stop the cell cycle, then recruit proteins to repair the DNA. Sometimes DNA cannot be repaired, and so p53 will trigger apoptosis, programmed cell death, instead of allowing the cell to continue the cell cycle.

P21 is produced when there is enough p53 in the cell. P21 acts directly on cyclin and cdks by binding to the cyclin/cdk complex, inhibiting their ability to phosphorylate and progress the cell cycle. As p53 detects problems in the cell, the concentration of p53 and p21 increases, preventing the cell cycle from continuing.

Rb primarily monitors the cell size. When the cell is too small, rb will be active and will bind to transcription factors, specifically called E2F, that help to produce proteins needed for the G1/S checkpoint. As the cell grows it can spend energy phosphorylating rb, changing its shape and forcing it to release E2F. Now that E2F is free, it can begin the transcription of the proteins necessary to progress the cell cycle.

Cell Cycle - Key takeaways

  • The cell cycle is made of two main phases: the interphase and the mitotic phase.
  • Interphase has 3 sub-phases: G1 that prepares the cell for the S phase, S phase replicates DNA, and G2 which prepares the cell for cell division during the mitotic phase.
  • The mitotic phase has mitosis and cytokinesis. Mitosis separates the duplicated DNA into the two new daughter cells and consists of 5 sub-phases: prophase, prometaphase, metaphase, anaphase, and telophase. Cytokinesis is when cell division finally occurs completing the cell cycle.
  • After completing the cell cycle, the cell may move into G0 where it only performs its function and does not complete a new cell cycle. Nerve cells and cardiac cells are prime examples of G0.

Final Cell Cycle Quiz

Cell Cycle Quiz - Teste dein Wissen

Question

Histones are:


Show answer

Answer

Proteins that DNA wraps around to make nucleosomes

Show question

Question

Homologous chromosomes are defined as:

Show answer

Answer

Chromosomes that hold the same genes at the same locus. 

Show question

Question

Prokaryotic chromosomes are stored in the:

Show answer

Answer

Nucleoid

Show question

Question

Humans have how many Chromosomes?

Show answer

Answer

46 total chromosomes,  23 pairs of homologous chromosomes.

Show question

Question

What is the relationship between chromatin and chromosomes?

Show answer

Answer

Chromatin folds around scaffolding proteins to make Chromosomes.

Show question

Question

What is the relationship between nucleosomes and chromatin?

Show answer

Answer

When nucleosomes are wrapped around themselves many times, they are compacted into chromatin.

Show question

Question

What is the relationship between histones and nucleosomes?

Show answer

Answer

When DNA wraps around histone proteins, together they form nucleosomes.

Show question

Question

Sex Chromosomes are:

Show answer

Answer

Homologous chromosomes that hold genes for sexual characteristics

Show question

Question

Choose the answer that is true for Sex Chromosomes.

Show answer

Answer

X Chromosomes are bigger than Y Chromosomes

Show question

Question

Each chromosome in a homologous pair comes from

Show answer

Answer

one of the organism's parents.

Show question

Question

What are gametes?


Show answer

Answer

Sex cells, like an egg or a sperm cell.

Show question

Question

What types of cells are haploid (1n), what types of cells are diploid (2n)?


Show answer

Answer

Gametes are haploid, somatic cells are diploid

Show question

Question

A genome is:


Show answer

Answer

all the genetic material for an organism.

Show question

Question

What is a plasmid?


Show answer

Answer

Small circular fragments of DNA prokaryotes pick up from their environment. Often they can convey advantageous characteristics, like antibiotic resistance.

Show question

Question

What is the cell cycle?

Show answer

Answer

It is the life cycle of the cell as it prepares for cell division.

Show question

Question

Which of the following is NOT a reason a cell will enter G0?

Show answer

Answer

The cell automatically enters G0 as a regular part of interphase and will progress to G1 after a checkpoint

Show question

Question

What molecules are involved in the positive regulation of the cell cycle?

Show answer

Answer

Cyclins and Cyclin-dependent kinases

Show question

Question

Define positive regulation in relation to the cell cycle:

Show answer

Answer

Positive regulation progresses the cell cycle. It helps the cell move from one stage to the next: Ex. Cyclin and Cyclin-dependent kinases 

Show question

Question

Define negative regulation in relation to the cell cycle:

Show answer

Answer

Negative regulation stops the cell cycle from progressing. Ex: Rb, p53, and p21 prevent movement to the next phase when the cell is too small or the DNA is damaged.

Show question

Question

Which of the following is NOT involved in negative cell cycle regulation?

Show answer

Answer

Cyclin E, helps the cell progress from G1 to S phase.

Show question

Question

When are the cell cycle checkpoints?

Show answer

Answer

  1. Between G1 and S phase.
  2. Between G2 and Mitosis.
  3. During Metaphase before Anaphase in Mitosis.

Show question

Question

True or False, Cyclins are ever-present in the cell and wait to be activated.

Show answer

Answer

False, cyclins are produced and increase in concentration during the cell cycle.

Show question

Question

True or False, Cyclin-dependent kinases are ever-present in the cell and wait to be activated.

Show answer

Answer

True, the cdks are always present in the cell but cannot be activated without the corresponding cyclin, and then must be phosphorylated to activate.

Show question

Question

What does the cell check for during the metaphase checkpoint before progressing to anaphase?

Show answer

Answer

That the spindle microtubules are connected properly to each sister chromatid, so each new cell will have the correct amount of chromosomes.

Show question

Question

What are the two sub-phases of the mitotic phase? 

Show answer

Answer

Mitosis and cytokinesis

Show question

Question

What are the phases of mitosis in order?

Show answer

Answer

Prophase, Prometaphase, Metaphase, Anaphase, Telophase

Show question

Question

What is the main concern of the cell during mitosis?

Show answer

Answer

The separation of the DNA chromosomes.

Show question

Question

What is the main concern of Cytokinesis?

Show answer

Answer

Separating the cell into two daughter cells.

Show question

Question

A cell plate will form in plant cells during what phase?

Show answer

Answer

Cytokinesis

Show question

Question

During cytokinesis in an animal cell, how does the cell split?

Show answer

Answer

The cell forms a microtubule contractile ring to make a cleavage furrow.

Show question

Question

Fill in the blank: Metaphase is easily identifiable because the chromosomes_______

Show answer

Answer

align in the center of the cell on the metaphase plate.

Show question

Question

What do kinetochores do during mitosis?

Show answer

Answer

Kinetochores form on each sister chromatid, allowing the spindle microtubules to pull the chromatids apart into new nuclei.

Show question

Question

What organelles build the spindle microtubules?

Show answer

Answer

Centrosomes

Show question

Question

The cell plate forms from what organelles?

Show answer

Answer

Golgi vesicles release enzymes structural proteins and glucose.

Show question

Question

Mitosis is sometimes called _________ meaning "cell nuclei movement"

Show answer

Answer

Karyokinesis

Show question

Question

What phase of mitosis do the cohesin proteins break down and the sister chromatids separate?

Show answer

Answer

Anaphase

Show question

Question

What protein causes the chromosomes to condense and become visible?

Show answer

Answer

Condensin

Show question

Question

Where are the kinetochores located?

Show answer

Answer

In the centromere of the chromosome for each sister chromatid.

Show question

Question

What three roles do the spindle microtubules play?

Show answer

Answer

1) separate the sister chromatids during anaphase

2) The polar microtubules elongate the cell in preparation for cytokinesis

3) The astral microtubules position the other microtubules in the cell.

Show question

Question

What happens to the membranous organelles (Nucleus, Golgi Apparatus, Endoplasmic Reticulum) during mitosis?

Show answer

Answer

They break apart into vesicles and move to the outskirts of the cell, making way for the chromosomes to separate.

Show question

Question

What is another name for mitosis?

Show answer

Answer

Karyokinesis, meaning cell nuclei movement.

Show question

Question

What role does the kinetochore play during mitosis?

Show answer

Answer

Kinetochores attach the chromosomes to the spindle microtubules, allowing the chromosomes to be moved and pulled apart by the spindles

Show question

Question

At the end of mitosis, how much DNA do each new nuclei possess?

Show answer

Answer

A full set of DNA, (2n/diploid)

Show question

Question

What is the equivalent to binary fission in eukaryotes?

Show answer

Answer

The Cell Cycle

Show question

Question

What are the four steps to binary fission?

Show answer

Answer

DNA replication, Cell Growth, Genome Segregation, Cytokinesis

Show question

Question

How is cytokinesis during binary fission similar to cytokinesis in an animal cell?

Show answer

Answer

During binary fission, a ring of FtsZ proteins forms a contractile ring and cleavage furrow. This is similar to the contractile ring of actin filaments and cleavage furrow in animal cells.

Show question

Question

How is cytokinesis during binary fission similar to cytokinesis in a plant cell?


Show answer

Answer

FtsZ proteins trigger the synthesis of a new cell wall and plasma membrane, creating a septum. This is similar to the Golgi vesicles building a cell plate during plant cytokinesis.

Show question

Question

What is the origin, in regards to binary fission?

Show answer

Answer

The origin is the site where DNA replication begins. It is near where the prokaryotic chromosome is attached to the plasma membrane.

Show question

Question

How does the prokaryotic chromosome get segregated?

Show answer

Answer

As the cell grows, the attachment point of the duplicating chromosomes get separated to opposite sides of the cell, taking chromosomes with it.

Show question

Question

How are plasmids segregated during binary fission?

Show answer

Answer

The duplicated plasmids are haphazardly distributed during genome segregation, leading to variation in the daughter cells.

Show question

Test your knowledge with multiple choice flashcards

Histones are:

Prokaryotic chromosomes are stored in the:

Choose the answer that is true for Sex Chromosomes.

Next

Flashcards in Cell Cycle144

Start learning

Histones are:


Proteins that DNA wraps around to make nucleosomes

Homologous chromosomes are defined as:

Chromosomes that hold the same genes at the same locus. 

Prokaryotic chromosomes are stored in the:

Nucleoid

Humans have how many Chromosomes?

46 total chromosomes,  23 pairs of homologous chromosomes.

What is the relationship between chromatin and chromosomes?

Chromatin folds around scaffolding proteins to make Chromosomes.

What is the relationship between nucleosomes and chromatin?

When nucleosomes are wrapped around themselves many times, they are compacted into chromatin.

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