Cell Cycle

A cell cycle is a series of events that takes place in a cell as it grows and divides. A cell spends most of its time in what is called interphase, and during this time it grows, replicates its chromosomes, and prepares for cell division. The cell then leaves interphase, undergoes mitosis, and completes its division. The resulting cells, known as daughter cells, each enter their own interphase and begin a new round of the cell cycle.

The cell cycle is the process a cell will go through to replicate all of its material and divide itself from one cell into two identical cells. While this is commonly known as Mitosis, in fact Mitosis is just one stage of the cell cycle. In this article, we will look at the different stages of the cell cycle and what happens in each stage. We will also consider the regulation of the cell cycle, and look at some examples of when this goes wrong.

Phases of the Cell CycleThe Cell Cycle is a 4-stage process consisting of Gap 1 (G1), Synthesis, Gap 2 (G2) and Mitosis. An active eukaryotic cell will undergo these steps as it grows and divides. After completing the cycle, the cell either starts the process again from G1 or exits the cycle through G0. From G0, the cell can undergo terminal differentiation.
G1 phase

• Metabolic changes prepare the cell for division.
• Cell increases in size
• Cellular contents duplicated
• At a certain point (restriction point) the cell is committed to division and moved to S phase.

S phase

• DNA synthesis replicates the genetic material.
• Each of the 46 chromosomes (23 pairs) is replicated by the cell

G2 phase

• Metabolic changes assemble the cytoplasmic material required for mitosis and cytokinesis.

M phase

• Mitosis followed by Cytokinesis (cell separation)
• Formation of two identical daughter cells

Phases of Mitosis

Mitosis is a form of eukaryotic cell division that produces two daughter cells with the same genetic component as the parent cell. Chromosomes replicated during the S phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome. In actively dividing animal cells, the whole process takes about one hour.

The replicated chromosomes are attached to a ‘mitotic apparatus’ that aligns them and then separates the sister chromatids to produce an even partitioning of the genetic material. This separation of the genetic material in a mitotic nuclear division (or karyokinesis) is followed by a separation of the cell cytoplasm in a cellular division (or cytokinesis) to produce two daughter cells.
In some single-celled organisms mitosis forms the basis of asexual reproduction. In diploid multicellular organisms sexual reproduction involves the fusion of two haploid gametes to produce a diploid zygote. Mitotic divisions of the zygote and daughter cells are then responsible for the subsequent growth and development of the organism. In the adult organism, mitosis plays a role in cell replacement, wound healing and tumour formation.
Mitosis, although a continuous process, is conventionally divided into five stages: prophase, prometaphase, metaphase, anaphase and telophase.

Prophase

• Prophase occupies over half of mitosis.
• The nuclear membrane breaks down to form a number of small vesicles and the nucleolus disintegrates.
• A structure known as the centrosome duplicates itself to form two daughter centrosomes that migrate to opposite ends of the cell.
• The centrosomes organise the production of microtubules that form the spindle fibres that constitute the mitotic spindle.
• The chromosomes condense into compact structures.
• Each replicated chromosome can now be seen to consist of two identical chromatids (or sister chromatids) held together by a structure known as the centromere.

Prometaphase

• The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid-line of the cell – at right-angles to the axis formed by the centrosomes.
• This region of the mitotic spindle is known as the metaphase plate.
• The spindle fibres bind to a structure associated with the centromere of each chromosome called a kinetochore.
• Individual spindle fibres bind to a kinetochore structure on each side of the centromere.
• The chromosomes continue to condense.

Metaphase

• Chromosomes align at the metaphase plate of the spindle apparatus.

Anaphase

• The shortest stage of mitosis.
• The centromeres divide, and the sister chromatids of each chromosome are pulled apart – or ‘disjoin’ – and move to the opposite ends of the cell, pulled by spindle fibres attached to the kinetochore regions.
• The separated sister chromatids are now referred to as daughter chromosomes. (It is the alignment and separation in metaphase and anaphase that is important in ensuring that each daughter cell receives a copy of every chromosome.)

Telophase

• The final stage of mitosis, and a reversal of many of the processes observed during prophase.
• The nuclear membrane reforms around the chromosomes grouped at either pole of the cell,
• the chromosomes decondense (uncoil) and become diffuse,
• the spindle fibres disappear.

Cytokinesis is the process of the parent cell becoming 2 daughter cells. These daughter cells contain identical genetic information. In plants a cell plate forms along the line of the metaphase plate; in animals there is a constriction of the cytoplasm. The cell then enters interphase – the interval between mitotic divisions. It is considered a separate step to mitosis.
The stages in the cell cycle between one mitosis and the next, which includes G1, S and G2, is known as interphase.

Meiosis I

Meiosis is the form of eukaryotic cell division that produces haploid sex cells or gametes (which contain a single copy of each chromosome) from diploid cells (which contain two copies of each chromosome). The process takes the form of one DNA replication followed by two successive nuclear and cellular divisions (Meiosis I and Meiosis II). As in mitosis, meiosis is preceded by a process of DNA replication that converts each chromosome into two sister chromatids.

Meiosis I

Meiosis I separates the pairs of homologous chromosomes.

In Meiosis I a special cell division reduces the cell from diploid to haploid.

Prophase I

The homologous chromosomes pair and exchange DNA to form recombinant chromosomes. Prophase I is divided into five phases:

• Leptotene: chromosomes start to condense.
• Zygotene: homologous chromosomes become closely associated (synapsis) to form pairs of chromosomes (bivalents) consisting of four chromatids (tetrads).
• Pachytene: crossing over between pairs of homologous chromosomes to form chiasmata (sing. chiasma).
• Diplotene: homologous chromosomes start to separate but remain attached by chiasmata.
• Diakinesis: homologous chromosomes continue to separate, and chiasmata move to the ends of the chromosomes.

Prometaphase I

• Spindle apparatus formed, and chromosomes attached to spindle fibres by kinetochores.

Metaphase I

• Homologous pairs of chromosomes (bivalents) arranged as a double row along the metaphase plate.
• The arrangement of the paired chromosomes with respect to the poles of the spindle apparatus is random along the metaphase plate. (This is a source of genetic variation through random assortment, as the paternal and maternal chromosomes in a homologous pair are similar but not identical.
• The number of possible arrangements is 2n, where n is the number of chromosomes in a haploid set. Human beings have 23 different chromosomes, so the number of possible combinations is 223, which is over 8 million.)

Anaphase I

• The homologous chromosomes in each bivalent are separated and move to the opposite poles of the cell

Telophase I

• The chromosomes become diffuse and the nuclear membrane reforms.

Cytokinesis
The final cellular division to form two new cells, followed by Meiosis II. Meiosis I is a reduction division: the original diploid cell had two copies of each chromosome; the newly formed haploid cells have one copy of each chromosome.

Meiosis II

Meiosis II separates each chromosome into two chromatids.

The events of Meiosis II are analogous to those of a mitotic division, although the number of chromosomes involved has been halved.
Meiosis generates genetic diversity through:

• the exchange of genetic material between homologous chromosomes during Meiosis I
• the random alignment of maternal and paternal chromosomes in Meiosis I
• the random alignment of the sister chromatids at Meiosis II

Meiosis in females

Regulation

The progression of cells through the cell cycle is controlled by checkpoints at different stages. These detect if a cell contains damaged DNA and ensure those cells do not replicate. The Restriction point (R) is located at G1 and is a key checkpoint. The vast majority of cells that pass through the R point will end up completing the entire cell cycle. Other checkpoints are located at the transitions between G1 and S, and G2 and M.

If damaged DNA is detected at any checkpoint, activation of the checkpoint results in increased protein p53 production. p53 is a tumour suppressor gene that stops the progression of the cell cycle and starts repair mechanisms for the damaged DNA. If this DNA cannot be repaired, then it ensures the cell undergoes apoptosis and can no longer replicate.
This cell cycle is also closely regulated by cyclins which control cell progression by activating cyclin-dependent kinase (CDK) enzymes.

An example of a tumour suppressor protein would be retinoblastoma protein (Rb). Rb restricts the ability of a cell to progress from G1 to S phase in the cell cycle. CDK phosphorylates Rb to pRb, making it unable to restrict cell proliferation. This allows cells to divide normally in the cell cycle.

Apoptosis

• Apoptosis helps to regulate animal cell number
• The number of the cells is tightly regulated by controlling the rate of cell division, but also the rate of cell death
• Apoptosis is a programmed cell death
• The molecular machinery responsible for apoptosis involves a family  of proteases called CASPASES
• These enzymes are made as inactive precursors  
• Two types of signals induce apoptosis : intrinsic or extrinsic