Cell Cycle, Cell Cycle Phases, and Metaphase

Cell cycle is the sequential process taking place to regulate the growth of organism; cell divides to produce a genetic replica and enters the stage of cell growth.

Cell growth involves the synthesis of organic material and integrates information across its counter parts for synchronous development of the whole body.

The cell synthesis phase lasts till a cell reaches its maturity; on initiation the cell again divides to produce new cell and the process continues. Cell cycle is a sequential development of cell between two cell divisions.

The cycle is genetically controlled and are programmed in every cell and are specific for each region.

Varied species has variable time length of cell cycle decided by physiological and influences pertaining to their niche.

Two Phases of cell cycle are: INTERPHASE and MITOTIC PHASE. INTERPHASE involves G1, synthesis and G2 phase; chromosomal replication and development is regulated by the phase; determines the quality and quantity of chromosome entering the daughter cells and a balance is maintained by the phase.

Karyokinesis and Cytokinesis division, segregation of chromosome and cell takes place during MITOTIC PHASE.

The notable feature of cell cycle is eukaryotic organisms though diverse and distinct have a common type of cell division over the Kingdom of Eukaryotes is a scientific wonder and research have emphasized that timing of a cell entering the cell cycle is essential in cell cycle regulation.

History of Cell Cycle

The history of mitosis dates back to 18th and 19th century where the aid from microscope and visibility of cell division under the microscope supported the discovery of the cell division.

The discovery was earlier than the DNA discovery was a breakthrough in the scientific community as it answered the most intriguing question of Humans “How do we grow? Develop? Reproduce? What is the driving factor for the growth? How do we resemble our parents?” etc.,

Before the discovery of cell division there were many theories on how the cells are related to the overall development of an organism’s lifecycle.

One of which was Rudalph Virchow’s theory of cell: “Omnis cellula e cellula” which states that a cell originates from a pre-existing cell.

Walther Flemming discovered and published a detailed book on cell division in 1882 after discovering cell division in 1879.

He named it “Mitosis” after the Greek word Mito – “Wrapping thread” owing to the thread like appearances of the chromosomes.

He conducted a detailed study and deduced staining techniques to understand cell cycle and named the stages of each division as Prophase, metaphase, Anaphase and Telophase.

The cell division was identified in Salamander’s embryo. Flemming supported Virchow’s cell theory with precision and stated that “Omnis nucleus e nucleo” which states that a nucleus origin from a pre – existing nucleus and highlighting the chromosomal segregation and laid foundation for the theory of inheritance where the chromosomes play an important role carrying the genetic information from the parent to the offspring.

Cell Cycle Phases

The cell cycle is common for all eukaryotic organisms; travelling through 2 major phases based on the cell division:

INTERPHASE and MITOTIC PHASE. Interphase consists of 3 phases Gap 1 phase, Synthesis Phase and Gap 2 Phase.

Similarly, mitosis has four phases Prophase, metaphase, anaphase, and telophase.

The development of cells through these phases are influenced and facilitated by heterodimeric protein kinases – Cyclin and Cyclin Dependent Kinases.

Mitotic Phase

The changes in above phases are minimal or not clearly visible in microscopes whereas the changes in M Phase are easily detectable.

The phase has 4 parts in which the division takes place systematically and continuously.

The cell stages are easily visible in plant parts as the specialized dividing region – MERISTEM is prevalent in roots and shoots are continuously dividing providing a mechanical support and functional integrity to the plants.

The 4 phases are: Prophase, Metaphase, Anaphase and Telophase.

Each phase has a distinctive change to be identified and Eukaryotic cells replicates in the same order in most of the organisms.

Prophase: The prophase is marked by chromosomal condensation and disintegration of cellular components and assembly of cytoskeletons for cell division. RNA synthesis is inhibited.

Metaphase: Nuclear membrane is eliminated completely chromosomes are completely condensed. The cytoskeleton – spindle fibers attach to the kinetochores. The chromosomes are aligned in the equatorial plate.

Anaphase: Chromosomal split forms daughter chromatids; travels to the opposite poles. The chromosomes are V – Shaped as they are dragged to the opposite sites.

Telophase: Microtubules disappear and chromosomes decondense to chromatin mass. Nuclear envelope starts to form. The disintegrated organelles form again.

Metaphase

Metaphase events are not clearly deduced but it mainly concerns in the arrangement of the chromatids in the equatorial plane for even distribution of the genetic material among daughter cells.

The Kinetochore – Spindle fiber complex does not hold the chromosome at equatorial plate.

The process of aligning chromatids at a single plate is the congression.

The mechanism of congression is still unknown and so remains the initiation of METAPHASE.

Metaphase uses GTP to maintain a steady state and end of the phase is a transitory period and essential point in cell division is well known to dephosphorylations induces changes in cell regulators – CYC – CDK complex and initiates APC\C.

Pro-Metaphase

Chromosomal condensation completes in prometaphase.

Chromosomal segregation is initiated in this phase by the attachment of spindle fibers from centrosomes in animal cells as plant cell lacks centrosomes.

Cellulosic cell wall of plants does not make the cell dynamic to organized into spherical shape for the sister chromatids to produce into a new cell; plants organize a special band called Prophase band (PPB) perpendicular to the site of equatorial plate formation of chromosomes.

The PPB consists of actin and other microtubules coordinates with kinetochores and chromatin to assemble the chromosomes in the metaphase plate for segregation.

Additional microtubules arise just outside of the nuclear membrane after complete disintegration in early prometaphase.

Attachment of spindle fibers are made sure in prometaphase and are checked by checkpoints and relies on spindle attachment techniques and prerequisites of spindle formation.

Metaphase, Spindle Fibers and Functions

Spindle fibers are connecting machines contributes to the mechanical support to the cellular dynamic and preserves structural integrity of a cell.

Spindle fibers are protein complexes formed and named by the protein such as Dynein, Kinesin, Actin, Tubulin etc., are varied among the living system; has an indispensable role in ensuring the survival.

The fibers are nucleated and attach to the kinetochores contributes to the cellular dynamics and mitotic dynamic (i.e.) chromosomal segregation and shape perseverance.

The spindle fibers are bipolar in origin from centrosomes of animals and PPB in plants associates with kinetochores by specific mechanism of “Search and Capture”

Oscillation of microtubules in the cytoplasm in search of kinetochores of the chromosomes from opposite sides to hold them in the mitotic plate and pass to anaphase.

The spindle and the chromosomes are dynamic structures which constantly changes its position.

The kinetochores must be appropriately attached to its side and the opposite sister chromatid kinetochore must bind to the opposite pole to ensure equal distribution of the genetic material.

The microtubule when attached to a kinetochore many other microtubules branching from the existing microtubule or formation from the kinetochore attaches along the existing microtubule forming spindle fiber.

The spindle fiber attachment is succeeded by CDK – CYC complex and other supporting proteins such as Augnin in animals or generally a RAN – GTP associated pathway ensures the connection of chromosomes.

SAC, Metaphase, and Spindle Fibers

Spindle Assembly Checkpoint (SAC) is the main gateway for a cell to cross the metaphase supported by the kinases of kinetochores.

The kinases ensure attachment of all chromatids to its respective poles.

Kinetochore’s orientation is an initial property where it ensures a proper attachment to the respective spindle fibers by their bipolar coordination.

The spindle fibers arise from both poles to capture chromatids are driven by motor present in kinetochore on binding tends to direct the chromatids to the point of origin.

The mitotic spindle attachment creates an active motility with the spindle fibers and kinetochores and becomes unstable.

Stability is attained when the sister kinetochore attaches to the opposite microtubule which creates a tension enabling chromatids to oscillate from a pole to other.

SAC as said involves kinases to ensure the chromatid connectivity to proceed to next phase is regulated by a cascade.

The main principle is that the attached kinetochores support Anaphase promoting complex or cyclosomes to proceed to the next phase.

When a polyubiquitination by an APC/C are inhibited the cell division is temporarily held back to ensure the connection of the kinetochore which completes the cascade and ensures the entry to ANAPHASE.