The Cell Cycle – Interphase & Mitosis

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Summary

  • The cell cycle is made up of two main stages: interphase and mitosis
  • During interphase, cells are duplicating their material and synthesising proteins to prepare to divide.
  • Interphase encompasses 3 phases: G1, S and G2. During S phase, DNA is replicated.
  • Mitosis encompasses prophase, prometaphase, metaphase, anaphase telophase. During these phases, the nuclear envelope disappears, the mitotic spindle forms, chromosomes condense and are lined up at the metaphase plate, and separated by being pulled to each side of the cell
  • During the final stages of the cell cycle, cytokinesis occurs, where the cytoplasmic contents are separated into two daughter cells.

The cell cycle describes a sequence of reactions that results in the growth of the cell and replication of the genetic material to make two identical daughter cells. These events are tightly regulated and precisely timed, and can be grouped into two phases: interphase and the mitotic (M) phase. During interphase, the cell grows and DNA is replicated, and during the mitotic phase, the cell divides and the DNA is distributed to the daughter cells. A typical human cell cycle takes around 24 hours, but the cell cycle can be drastically different in different cell type.

Interphase

Most of the time in the cell cycle is spent in a preliminary phase: interphase. Interphase can be further subdivided into three phases: G1, S and G2. DNA replication occurs in the ‘S’ phase (the ‘Synthesis’ phase). The ‘G’ phases (also called gap phases) represent periods of growth in preparation for the division of the cell. Checkpoints also exist at these phases to ensure the cell is ready to divide.

G1 phase

The first phase of interphase and the cell cycle is called G1. During G1, the cell is preparing to replicate DNA by synthesising the mRNAs and proteins required to execute the future steps. The cell usually grows larger, and some organelles are copied.

S phase

During the S phase, all the genetic information in the cell is copied by the process of DNA replication. This process of replication generates sister chromatids, which are identical pairs of chromosomes. These sister chromatids are attached to each other by a centromere. A centromere is a specialised sequence of DNA that links the sister chromatids and is important throughout mitosis.

 G2 phase

The final phase of interphase is the G2 phase. During this time, the cell undergoes additional growth, replenishes energy stores and prepares and reorganises the cytoplasmic components for division, including duplicating some organelles and dismantling the cytoskeleton. G2 ends when mitosis begins.

Mitosis (M)

The mitotic phase describes a series of processes during which the replicated DNA condenses into visible chromosomes, which are aligned, separated, and passed on to two new daughter cells. The movement of chromosomes is orchestrated by specialised structures called microtubules. Mitosis can be further subdivided into four main phases: prophase, prometaphase, metaphase, anaphase and telophase (PPMAT). Sometimes, prometaphase is not considered a separate phase. These phases result in the division of the cell nucleus (also called karyokinesis), and then the separation of the cytoplasm to form two new daughter cells (also called cytokinesis).

Prophase

The first phase of mitosis is called prophase. During prophase, the chromosomes start to condense the nuclear envelope breaks down, and the associated organelles break up and move towards the edge of the cell. A structure called the mitotic spindle also starts to form here. This structure is made of microtubules and is important in moving chromosomes around during mitosis. The mitotic spindles extend from either side of the cell (at opposite poles).

Prometaphase

Prometaphase is sometimes not classified as an independent step and can be referred to as late prophase. During prometaphase, the processes begun in prophase continue: the nuclear envelope is broken down, and the chromosomes are fully condensed. The mitotic spindle grows and begins to organise the chromosomes. A special structure called the kinetochore appears at this stage. The kinetochore is a protein structure is important for linking the chromosomes to the mitotic spindle and is assembled on the centromere.

Metaphase

During metaphases, the mitotic spindle facilitates the movement of chromosomes such that they align along the centre of the cell, at the metaphase plate. At this point, sister chromatids are still attached to one another. Following metaphase, there is an important checkpoint called the spindle checkpoint. This ensures anaphase will not proceed unless all the chromosomes are at the metaphase plate and attached to microtubules (by the kinetochore). This is a hugely important checkpoint ensuring that each daughter cell receives the correct number of chromosomes.

Anaphase

When the chromosomes are properly aligned, anaphase can proceed. Anaphase is the process during which the sister chromatids separate at the centromere and are pulled to the edge of the cell. These chromatids are now referred to as chromosomes.

Telophase

During telophase, the spindle disappears and a new the nuclear envelope forms around the chromosomes. The chromosomes also start to decondense as cytokinesis is taking place.

Cytokinesis

Cytokinesis completes the cell cycle, and usually overlaps with the final stages of mitosis. Cytokinesis involves in the physical separation of the cytoplasm and its components into daughter cells. This occurs when a ring of cytoskeletal fibres (called the contractile ring) form at the centre of the cell, making an indentation called the cleavage furrow. This ring tightens, eventually pinching the cell enough that it separates two to give two new daughter cells.

Cytokinesis is more complex in plant cells, which have a cell wall. Dividing plant cells overcome this by creating a structure called the cell plate, which is made from vesicles containing plasma membrane and cell wall components. The cell plate enlarges until it merges with the cell walls. This divides the cell in two and allows the cell wall to be regenerated.

G0 phase and cell cycle exit

Not all cells are actively dividing. A cell in the G0 phase is said to be in a resting phase, and these cells are also called quiescent. This means it is not dividing or preparing to divide. Cells can enter G0 temporarily until there is a signal to divide, or can remain in G0 indefinitely. Examples of cells in G0 include neurons, which are metabolically active but not dividing.

Cell cycle regulation – checkpoints

At several points in the mitotic cell cycle, a checkpoint operates. These checkpoints regulate the progression of the cycle, ensuring mistakes are not passed on to the daughter cells. These key checkpoints occur at the end of G1, between G2/M and during metaphase. Cell cycle checkpoints are regulated by cell-signalling proteins.

At the G1 checkpoint, two features are checked: whether the conditions are appropriate for proceeding with the cell cycle, and DNA damage. The cell will only pass the checkpoint when it is large enough and has enough energy, and also that the external conditions are favourable for division. The cell also checks for DNA damage, and the cycle will not proceed if damaged DNA is detected, as there would be negative consequences if the daughter cells inherited damaged genetic material. G1 also contains a special checkpoint called the restriction point, the point at which the cell irreversibly commits to entering the cycle.

At the G2/M checkpoint, the cell ensures the chromosomes have been replicated correctly.

The metaphase checkpoint, also known as the spindle checkpoint, ensures that the cell cycle will not proceed until all the sister chromatids are properly attached to the mitotic spindle.

Further reading and references:

[1]. https://commons.wikimedia.org/wiki/File:Chromosomes_during_mitosis.svg Image sister chromatids

[2]. https://cnx.org/contents/GFy_h8cu@9.87:1tJ55Ot6@7/The-Cell-Cycle Image cell cycle

[3]. https://www.nature.com/articles/nrm3819 Image mitosis detail

[4]. https://www.youtube.com/watch?v=pOsAbTi9tHw

[5]. https://www.youtube.com/watch?v=7NM-UWFHG18

[6]. https://www.nature.com/scitable/topicpage/eukaryotes-and-cell-cycle-14046014

[7]. https://www.nature.com/scitable/topicpage/mitosis-and-cell-division-205

[8]. https://bscb.org/learning-resources/softcell-e-learning/cell-cycle-control/