Cell Cycle and Cell Division: The Mitosis

“Omnis cellula-e-cellula,” i.e., every cell is derived from a [pre-existing] cell.                                                                                Rudolf Virchow (German pathologist) 1858

However, the credit for the theory of the origin of cells goes to Virchow; he was not the first person to point out this theory. In 1852 a German neuroanatomist and embryologist, Robert Remak, pointed out that cell division accounted for the multiplication of cells to form tissues.

Why do cells divide?

Cell division is the only way to make more cells. All organisms, from unicellular to multicellular, reproduce or repair by cell division. The cell divides to maintain a high surface area to volume ratio so more substances can diffuse across the membrane.

How do cells divide?

Cells perform an orderly sequence of events in which it duplicates their contents and then divide. This orderly sequence of events of duplication and division is called Cell Cycle. Cell division in unicellular organisms like yeast and bacteria produces a new organism, but complex sequences of cell divisions are required to produce a new organism in multicellular organisms. The minimum set of events that a cell must undergo before division are:

DNA replication: Two complete copies of DNA are synthesized to produce identical daughter cells.

Chromosome segregation: The replicated DNA is distributed accurately into the daughter cells.

Organelle duplication: In addition to the DNA, cell organelles and macromolecules duplicate; otherwise, it will decrease after every division. Each step of duplication and division is precisely controlled, which is required to form identical daughter cells. These duplication and division events are called the cell cycle.

The Cell Cycle

  • The fundamental function of cell division is to precisely replicate the DNA and divide it into the daughter cells. These two functions are attributed to the two significant cell cycle phases.
  • The first phase is the I phase (I = interphase). In this phase, the DNA replicates, i.e., identical copies of DNA are formed. This phase requires 10-12 hrs and occupies about half of the cell cycle time in a typical mammalian cell. All organelles and macromolecules also synthesize in this phase.
  • The I-phase is divided into three sub-phases G1, S, and G2. A mammalian cell spends about 23 hrs of 24 hours in this phase.
  • The duplicated DNA is distributed equally into the daughter cells in the second phase. This phase is called the M phase (M = mitosis). It requires about 1 hr in a mammalian cell.
  • G1 and G2 are gap phases between S and M-phases in which cells grow by multiplying their macromolecules and organelles. The gap phases also provide time to monitor internal and external factors to ensure the preparation is complete to proceed into the actual division process.
  • If extracellular conditions are unfavourable, cells enter a temporary resting phase called the quiescent or G-zero (G0) phase, which may last for days, weeks, or even years before resuming proliferation.
  • In the S-phase, DNA replication and centriole duplication take place.
  • In the early division of Xenopus laevis and Drosophila fertilized eggs, no detectable G1, and G2- phases are observed. In these cells, S-phase alternates with M-phase. The zygote of Xenopus laevis takes about 90 minutes for its first division. Each of the subsequent 11 division cycles takes only 30 minutes.
  • Cell-division-cycle genes, or CDC genes, precisely control every phase of the cell cycle.
  • At the beginning of the M-phase of the cell cycle nuclear membrane degenerate. However, in yeast, it remains intact throughout the cell cycle.
  • After completion of the M-phase, a cell divides into two daughter cells. Both daughter cells have identical copies of the genetic material.

The significant events of the cell cycle

G1 phase:

  • Cell growth and organelle duplication.

S phase:

  • DNA replication, chromosome duplication, and centriole duplication.
  • A diploid cell replicates its DNA once and only once in each cell cycle.
  • The replicated DNA molecules are linked together by a protein complex. It is required for the orderly segregation of chromosomes during Anaphase.

G2 phase:

  • Cell growth and preparation for mitosis.

Prophase:

  • Condensation of chromosomal material. Chromosomes are seen to be composed of two chromatids attached at the centromere. The two chromatids attached by the centromere are called sister chromatids.
  • The mitotic spindle is assembled.
  • Golgi bodies and endoplasmic reticulum fragments and nuclear membrane dissembles.

Prometaphase:

  • The nuclear envelope breaks down. It marks the beginning of the prometaphase.
  • Microtubules attach to the kinetochore of each chromosome. Around 20-30 microtubules attach to the kinetochore from each pole in a mammalian cell.
  • There are three kinds of the microtubular organization during cell division—the first is kinetochoric, which attaches to the kinetochore of the centromere of the chromosomes; second, interpolar, which runs from pole to pole and third is astral, which radiates from each pole.
  • Chromosomes are moved back and forth. This movement is called congression.

Metaphase:

  • Chromosomes are aligned at the metaphase plate and attached to microtubules from both poles.

Anaphase:

  • Chromosomes split from the centromere.
  • Chromosomes start to move towards opposite poles (anaphase A).
  • Spindle poles also move apart, causing elongation of the cell (anaphase B).

Telophase:

  • Chromosomes cluster at spindle poles.
  • Chromosomes disperse.
  • Nuclear membranes assemble around each of the Chromosome clusters.
  • Golgi bodies and endoplasmic reticulum reform.
  • Cytokinesis produces two daughter cells.

Cytokinesis:

Animal cell-

  • Mitosis accomplishes the segregation of duplicated chromosomes, but a cell is divided into two daughter cells by cytokinesis.
  • At Anaphase, when chromosomes break at the centromere, a slight indentation appears at the metaphase plate as a cell furrow.
  • As the cycle progress, the cell furrow deepens. In the end, the surfaces of the cleavage furrow fuse with one another, splitting the cell into two.

Plant cell-

  • Cytokinesis begins with the cell plate formation in the middle of the cell and advances toward the ends.
  • The growing wall meets the existing lateral walls separating a cell into two.
  • The first sign of cell plate formation appears in the late Anaphase.

Cell cycle control:

Each step of the cell cycle is precisely controlled. Leland Hartwell and Ted Weinert formulated the concept of cell cycle checkpoints. These cell cycle surveillance mechanisms stop the progress of the cell cycle when DNA is not entirely replicated, any damage in the chromosomal DNA, and chromosomes are not correctly aligned. A system of sensors recognizes the DNA damage or cell abnormality and keeps the checkpoints activated throughout the cell cycle. These checkpoints delay the progress of the cell cycle and allow the repair mechanism to repair the damage. Once the damage is repaired, the cell cycle progresses to completion. If the damage is beyond repair, the checkpoint mechanism pushes the cell either into senescence (permanent cell cycle arrest) or death. The checkpoint mechanism is essential because a cell with damaged DNA can be transformed into cancer if allowed to divide.

Summary:

The cell cycle is a series of events that leads to the duplication and division of a cell. Animal cells show a wide variety of cell cycles, but the most common type is illustrated by the stratified epithelium. In describing the cell cycle, it is divided into different phases. Flemming named the process of the events during nuclear division mitosis. Mitosis begins with prophase, in which chromosomes condense to form a compact structure. The chromosomes are faithfully divided into the daughter cells into the subsequent phases of the cell cycle. Each daughter cell receives identical genetic material by the end of the ordered events.   

The Cell Cycle

References:

  • Karp, G., Iwasa, J., & Marshall, W. (2015). Karp’s Cell and Molecular Biology: Concepts and Experiments (8th ed.). Wiley.
  • Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell, Fourth Edition (4th ed.). Garland Science.
  • Md, T. P. D., Earnshaw, W. C., PhD, L. J., & Cmi, J. G. M. P. (2016). Cell Biology (3rd ed.). Elsevier.
  • Harris, H. (2000). The Birth of the Cell (Revised ed.). Yale University Press.

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