Table of Contents

Cell Cycle

The cell cycle is the series of events which takes place in a particular cell that divides it into two daughter cells and includes several crucial events, such as, the duplication of its DNA (i.e., replication of DNA) and some of its own organelles, and subsequently the separation of its cytoplasm and other components into two parts (called as daughter cells) in a process called cell division (the process by which any cell produces its own replica).

The frequency of cell division varies depending upon the different types of cell and its developmental stages. For example, cells divide rapidly as the embryo grows in size, during embryogenesis. Whereas, in an adult human body, almost all cells are terminally differentiated and are mostly non-dividing, (such as: neurons) or divide very infrequently, (such as: liver cells or hepatic cells that divide about once per year). These non-dividing cells are commonly termed as quiescent cells also there are some populations of adult human cells that are actively dividing, these include intestinal epithelial cells and adult-derived stem cells (such as: the bone marrow stem cells).

Eukaryotic cell cycle

Most of the eukaryotic cells undergo a reproductive cycle either to generate another copy of themselves or to generate gametes (sex cells), and in order to do so they require a complex mechanism to govern the safe and accurate replication of their much larger genomes (than prokaryotes), the eukaryotic cell cycle is divided into two main stages: interphase and the mitotic phase (which includes both karyokinesis and cytokinesis).

Overall, the process of cell division in eukaryotes (or eukaryotic cell cycle) is complex and highly regulated. The two broad stages (interphase and mitotic phase) of eukaryotic cell cycle and their sub-stages are elaborately discussed below:

Cell cycle phases

(1) Interphase

The period between the end of one mitotic phase and the beginning of the next mitotic phase is called interphase. It is the largest stage in the eukaryotic cell cycle. During interphase the cell gradually grows in size, and the nuclear DNA is also replicated. The cell normally grows and develops while preparing for cell division. For a cell to move from interphase to the mitotic phase, many internal and external conditions of the cell must be fulfilled. The three most important sub-stages of interphase are G1 phase, S phase, and G2 phase, these are discussed broadly below:

(i) G1 Phase of cell cycle (First Gap Phase/First Growth Phase)

The G1 phase (or first gap phase) is the first sub-stage of interphase stage of the eukaryotic cell cycle. The “G” in G1 phase is most often said to stand for “gap”, because these phase appears to be relatively inactive when observed with a microscope and so they are thought to be relatively inactive “gaps” in the cellular activity of the cell. Thus, G1 phase is called as the first gap phase.

However we all know today that the cell is quite active at the biochemical level during this phase of cell cycle. Therefore, it would be more accurate to say that the “G” stands for “growth” as at this phase cells are full of proteins and organelle production as well as the cell also grows and increases its size. Thus, this G1 phase can also be called as the first growth phase.

At this phase the cell produces many essential materials such as proteins and ribosomes also the cells that rely upon certain specialized organelles such as chloroplasts and mitochondria make a lot more of those organelles during G1 phase as well. Size of the cell also increases as it assimilates more material from its environment into its machinery for life.

The cell collects the building blocks of chromosomal DNA and the associated proteins as well as sufficient energy reserves in order to complete the task of replication of each chromosome in the nucleus at this stage. The cell physically grows much larger, copies its different organelles in this manner the cell grows in size and thus gradually makes the molecular building blocks which the cell will need in later steps to complete the cycle.

Furthermore, during the G1 stage of the cell cycle, DNA is checked/examined thoroughly for any damage and if any damage is found it is repaired for proper and correct processing of the cell cycle.

(ii) S Phase of cell cycle (Synthesis phase)

The S phase is called as the synthesis phase of the cell cycle as at this particular stage of the cell cycle mainly in eukaryotic cell cycle synthesis of new DNA occurs. Thus it can be inferred that the genome of an individual is being replicated during this phase, therefore at the end of S phase (or synthesis phase), the cell has twice the normal amount of DNA.

Throughout the complete interphase, the nuclear DNA within a cell remains in a semi-condensed chromatin configuration. In the S phase, the process of replication of DNA begins at specific sites of DNA called as origin of replication (ori), which are scattered in huge amount along the chromosomes.

At these specific sites of DNA certain proteins/enzymes (such as: helicase) open the DNA double helix and exposes it to some specific enzymes that carry out the process of DNA synthesis which usually move outward in both directions from the origins to copy the two strands of DNA.

The duplication of chromosomes also requires increased synthesis of the proteins, such as: histone proteins, that package the DNA into chromosomes. Different additional proteins also get deposited along the duplicated chromosomes during this S phase which results in a tight linkage, or cohesion, between them.

The replication of DNA proceeds through the mechanism that results in the formation of mainly two identical pairs of DNA molecules commonly called as sister chromatids, which are firmly attached to the centromeric region. Certain proteins called cohesins loop around these sister chromatids to keep them connected together.

The centrosome also gets duplicated during the S phase or the synthesis phase. The two centrosomes of homologous chromosomes gives rise to the mitotic spindle and the apparatus that manages the chromosomal movement during mitosis. For example, the centrosomes that are associated with a pair of rod-like objects, the centrioles, are positioned at right angles to each other. These centrioles help to organize the process of cell division. We should also note that the centrioles are usually not present in the centrosomes of other eukaryotic organisms, such as: plants and most fungi.

(iii) G2 Phase of cell cycle (Second Gap/Growth phase)

Same as the G1 phase of the cell cycle is called as the first gap phase or the first growth phase, the G2 phase is also called as the second gap phase or the second growth phase.

This G2 phase (or the second gap phase/second growth phase) occurs before M phase (or the mitotic phase). Thus, G2 phase is the gap phase between the S phase (or the synthesis phase) and M phase of the eukaryotic cell cycle.

The G2 phase of the eukaryotic cell cycle is characterized by lots of protein production. During this G2 phase many cells also check to make sure that both the copies of their DNA are correct and intact.

In the G2 phase, the cell again fills its energy stores and synthesizes proteins necessary for chromosome manipulation and movement. Some cell organelles also gets duplicated and the cytoskeleton is dismantled to provide resources for the mitotic phase. As in the G1 stage, during G2, the size of the cell increases and DNA damaged is repaired, if needed. During this G2 phase only the final preparations for the mitotic phase must be completed before the cell can enter the first stage of mitosis.

Therefore, these gap phases provide additional time for cell growth which usually requires much more time than is needed to duplicate and segregate the chromosomes normally. Thus, these gap phases also serve as important regulatory transitions where progression to the next cell-cycle stage can be controlled by a wide variety of intracellular and extracellular signals.

(iv) G0 Phase phase of cell cycle (quiescent phase)

All cells does not always adhere to the normal classic cell-cycle pattern in which a newly formed daughter cell immediately enters interphase, closely followed by the mitotic phase. It is a resting phase of the cell cycle. Cells in this particular G0 phase are not actively preparing to divide. The cell in this stage remains in a quiescent (inactive) condition which have exited the normal cell cycle, hence this G0 phase is also called as the quiescent stage. Some cells temporarily enter into this G0 phase until any external signal triggers the onset of the G1 phase of the cell cycle. Certain other cells that never or very rarely divide, such as: the mature cardiac muscle cells and the nerve cells, remains permanently in this G0 phase. Thus, G0 phase is a metabolic state which is meant only to maintain or store the daughter cell, but not to prepare them for any further divisions.

(2) M-phase (mitotic phase)

The M-phase (or the mitotic phase) in eukaryotic cell cycle is a multistep process in which the duplicated chromosomes are aligned, separated, and moved into two new identical daughter cells.

During mitotic phase, the parent cell passes through a complex series of different steps to ensure that each and every daughter cell get all the essential materials it needs to survive even including a copy of each chromosome. Once all the materials are properly sorted, the parent cell starts its division and gradually breaks down at the middle pinching its membrane in two.

The M-phase (or the mitotic phase) has several sub-phases, these are: prophase, metaphase, anaphase, telophase and cytokinesis. Among these five above mentioned sub-phases, prophase, metaphase, anaphase and telophase are commonly called as karyokinesis, which means that in these four sub-phase only the nucleus of the cell is divided not the cytoplasmic region of the cell. It is only at the cytokinesis phase of the mitosis (or mitotic phase/M-phase) stage of the eukaryotic cell cycle, where the complete cytoplasmic region of a cell is divided. Thus a complete cell gets divided into two parts, each forming an independent functional cell. All these sub-phases of M-phase/mitotic phase of the eukaryotic cell cycle are broadly discussed below:

(A) Karyokinesis:

Karyokinesis is the process in which the nucleus of the cell undergoes division resulting in the formation of two nucleus within the cell and this process of karyokinesis is completed through the passage of different sub-species, which are elaborately explained below:

1. Prophase

Prophase is the first sub-phase of the M-phase stage (or the mitotic phase) of the eukaryotic cell cycle. During this prophase several complex events occur which provides access to the chromosomes in the nucleus. The nuclear envelope gradually starts to break down, this is usually caused by phosphorylation of nuclear pore proteins and lamins, the intermediate filamentous cytoskeletal protein that provides a definite structure to the nuclear envelope by using the cell cycle regulatory protein M-cyclin/Cdk (Cyclin-dependent kinase proteins). Later, during telophase stage these proteins gets dephosphorylated to reform the nuclear envelope.

Additionally, the Golgi apparatus and the endoplasmic reticulum also breaks down into fragments and disperse to the periphery of the cell. The nucleolus gradually disappears and centrosomes begins to move to the opposite poles of the cell. The microtubules form the mitotic spindle and extend between the centrosomes by pushing them farther apart as the microtubule fibers lengthens due to dynamic instability. The sister chromatids starts to coil more tightly and become viewable under a light microscope. This complete process is actually facilitated by some proteins commonly called as condensins (ring-shaped proteins that further condense chromatin). Condensins are generally phosphorylated by M-cyclin/Cdk proteins (cyclin dependent kinase proteins) to further condense chromatin.

During the later part of prophase (often termed as prometaphase), many processes that already started in prophase continues to advance and culminate in the process of formation of a connection between the chromosomes and cytoskeleton. The residues of the nuclear envelope then disappears. The mitotic spindle further develops as lots of microtubules assemble together and stretch across the length of the former nuclear area. Chromosomes then gradually becomes more condensed and visually discrete. Each sister chromatid gets attached to spindle microtubules at the centromere region of the chromosome by a protein complex called as the kinetochore.

2. Metaphase

During the metaphase stage of the mitotic phase of eukaryotic cell cycle, all the chromosomes within the nucleus of the cell are aligned on the metaphase plate also called as the equatorial plane, at the middle of the two poles of the cell. The sister chromatids in this case are still tightly attached to each other by certain proteins called cohesins and the chromosomes are highly condensed.

3. Anaphase

During this anaphase stage of M-phase of the eukaryotic cell cycle, the sister chromatids which were present at the equatorial plane during the metaphase stage is separated, and for this, the cohesin proteins present during the metaphase stage to make the sister chromatids join tightly with one another must be removed first.

This process is regulated by another protein complex called as Anaphase Promoting Complex (APC). Before the anaphase stage starts, APC (Anaphase Protein Complex) remains in its inactive state i.e., it remains in dephosphorylated condition.

As soon as the anaphase stage of the mitosis (or mitotic phase/M-phase) begins, the APC (Anaphase Protein Complex) is phosphorylated by another group of specialized proteins called as M-cyclin/Cdk proteins (Cyclin dependent kinase proteins) and becomes active.

APC (Anaphase Protein Complex) acts as a ubiquitin ligase enzyme which means that it can add a small peptide called ubiquitin to proteins. When ubiquitin ligase enzymes add certain number of polymers of ubiquitin to proteins, this process is called as polyubiquitination and it serves to “tag” the proteins for degradation by the proteasome.

As the anaphase stage begins, the APC (Anaphase Protein Complex) polyubiquitinates the protein securin, causing this secruin to be degraded by the proteasome. This particular process of degradation of securing protein releases another protein called separase. This separase protein is actually an enzyme that physically breaks down the cohesin proteins that held the sister chromatids together.

Once these cohesin proteins are removed each sister chromatid are now called a chromosome which is pulled rapidly towards the centrosome to which its microtubule was attached. The cell then elongates as the non-kinetochore microtubules slide against one another at the equatorial plate (or metaphase plate) where they overlap.

4. Telophase

During this particular sub-phase (i.e., telophase) of the mitotic phase/M-phase of the eukaryotic cell cycle, each and every events that set up the duplicated chromosomes for mitosis during the first three sub-phases (i.e., prophase, metaphase and anaphase) are reversed. The chromosomes gradually reach to the opposite poles and then begins to decondense (or unravel). The mitotic spindles gets broken down into monomers which are used to assemble cytoskeletal components for each of the daughter cells. As mentioned earlier, lamins and nuclear pore proteins gets dephosphorylated which leads to the reformation of the nuclear envelope chromosomes.

(B) Cytokinesis

Cytokinesis can be considered as the second part of the mitotic phase/M-phase of the eukaryotic cell cycle. During this particular stage of the cell cycle, the cell division is completed by physically separating the cytoplasmic components of a specific cell into two daughter cells. Although all these stages of mitosis are similar in almost all eukaryotes but the process of cytokinesis have quite differences between those eukaryotes that have cell walls, such as: plant cells and those who lack cell wall, such as: animal cells.

In animal cells the process of cytokinesis begins at the onset of anaphase. A contractile ring which is made of actin filaments are formed within the plasma membrane at the former equatorial plane (or metaphase plate). These actin filaments gradually pulls the equator of the cell inward and forms a fissure. This fissure (or crack) thus formed is called as the cleavage furrow. This furrow then gradually deepens as the actin ring contracts and eventually the cell membrane and the complete cell (including the cytoplasm) gets cleaved in two parts, which are commonly called as daughter cells.

Cell cycle phases with diagram | Eukaryotic Cell Cycle