Monday, February 11, 2019

Cell Cycle, Mitosis and Meiosis

Realise the importance of the cell cycle

The cell cycle is basically just the life cycle of the cell: it grows, it replicates its DNA, it divides. Not all cells bother with the replication and division parts (I'm looking at you, neurons). Growth and division of cells has an integral role in growth and repair, as well as pathological disease processes such as cancer.

Understand the key steps in the cell cycle, mitosis & meiosis

Cell Cycle

The cell cycle consists of five main stages: G1, S, G2, M, and C. G1, S, and G2 are often grouped together as "interphase," while M and C are sometimes grouped together as mitosis. We will look at interphase first.

In G1 (first gap phase), cells grow and get ready for DNA replication. Some cells exit the G1 phase and enter G0, so that they will never have to undergo cell division. Some of these cells stay in G0 only temporarily, whereas others (I'm looking at you again, neurons) may stay in G0 for the rest of their lives.

In the S (synthesis) phase, the DNA is replicated. However, the number of chromosomes remains the same, as the number of chromosomes is determined by the number of centromeres (a constricted part near the middle of the chromosome), and the number of centromeres does not change. The nucleus becomes enlarged, presumably to accommodate the increased amount of DNA.

In the G2 (second gap) phase, there is further growth of cell and protein synthesis, as well as centrosome maturation, so that the cell can prepare for division. (Centrosomes are important in creating the spindle fibres, which are required in cell division.)

Mitosis

Once the cell has prepared for division, it's time to divide! As mentioned earlier, mitosis encompasses the M (mitotic) and C (cytokinetic) stages of the cell cycle.

The M phase can be broken down into several different phases: prophase, prometaphase, metaphase, anaphase, and telophase.

  • Prophase- Chromosomes condense so that the chromatids ("arms" of the chromosomes) can be seen clearly under a microscope. The centrosomes begin to form the mitotic spindle.
  • Prometaphase- The nuclear membrane disintegrates and the microtubules of the mitotic spindle attach to the chromatids. (Not all microtubules attach to chromatids. Those that do are called kinetochore microtubules, whereas the others, which branch out in a star-like fashion, are known as astral microtubules).
  • Metaphase- The chromosomes, attached to spindle fibres on either side, line up along the equator of the cell.
  • Anaphase- The spindle fibres "pull" sister chromatids to opposite ends of the cell. Note that at this stage there is twice the number of chromosomes, as each separated chromatid has its own centromere.
  • Telophase- Chromatids arrive at the spindle poles. The nuclear membrane re-forms around the chromatids, which become de-condensed.
Following the M phase, the C (cytokinesis) phase occurs. During the C phase, the cytoplasm divides. Once this is complete, the daughter cells move into G1 to start the cycle over again.

Meiosis

Meiosis is another type of cell division. Meiosis is used to create the ovum and sperm (a.k.a. germ cells). In meiosis, instead of creating two identical daughter cells with a full set of DNA, four daughter cells are formed, each with only half a set of DNA.

Meiosis involves two cell divisions. Meiosis I is reductional, meaning that the number of chromosomes (= number of centromeres) is halved between parent and daughter cells. Meiosis II is equational, meaning that the number of chromosomes (= centromeres) remains the same between parent and daughter cells. (Mitosis is also equational, in case you were wondering.)

Instead of explaining the whole process of meiosis (or processes, since there are two cell divisions), I'll simply compare each cell division to mitosis.

In meiosis I, prophase is pretty similar to mitosis, but something interesting happens. That something interesting is called crossing over. Homologous chromosomes (i.e. those with the same number but from different parents, such as two chromosome 14s) pair up and cross over at a point called the chiasma (plural: chiasmata). At the crossing over point, the two chromosomes in the pair can exchange segments of DNA. Crossing over allows for much greater genetic variety in the offspring. The rest of the stages are fairly similar to mitosis, with one main exception. In metaphase, chromosomes do not line up single-file along the equator. Instead, homologous chromosomes remain in their pairs, so that during anaphase, one member of each pair is pulled to one side of the cell, whereas the other member is pulled to the other side of the cell.

Meiosis II is pretty much identical to mitosis, except you are starting with fewer chromosomes.

Know chromosome structure and how chromosomes behave during the eukaryotic cell cycle

Chromosomes, as you should hopefully know by now, are made up of DNA. If cells are not about to divide, each chromosome is made up of a single molecule of DNA. As DNA is very long, it is important that it is wound up very tightly so that it can fit into the nucleus. In fact, chromosomes appear "banded" under a microscope due to the density of the packaging: dark bands are made up of tightly-packaged heterochromatin, whereas light bands are made up of loosely-packaged euchromatin. The more tightly packaged a specific region of DNA is, the less likely it will be transcribed.

Histones are proteins that are very important in packaging DNA. They are positively-charged due to the number of positively-charged amino acids (arginine, histidine, and lysine). The positive charge on histones helps them to bind to DNA, which is negatively-charged due to the phosphate groups in the backbone. A nucleosome consists of DNA wound around a core of histone molecules, and the DNA between nucleosomes is known as linker DNA. A nucleosome plus a special histone called histone H1 is known as a chromatosome.

When chromosomes are wound up like this, they eventually form a rod-like structure with a narrow bit towards the middle. The ends of the chromosomes are called telomeres, and these often grow shorter with cellular aging. The constricted bit in the middle, as mentioned earlier, is the centromere, which determines the number of chromosomes. The centromere also provides kinetochores, which microtubules bind to during cell division.

When DNA is replicated, the two DNA molecules form sister chromatids, which bind together in an X-like structure with a single centromere between them. Since there is only one centromere, the two DNA molecules are still considered to be one chromosome. Sister chromatids are joined together via proteins called cohesins, which are broken during anaphase of mitosis, allowing the chromatids to separate and move to opposite poles of the cell.

Meiosis is slightly more complicated, as there are two lots of divisions: dividing sets of homologous chromosomes before dividing sister chromatids. Cohesins are also used in meiosis, and they not only hold sister chromatids together but also hold homologous chromosomes together. A second important protein, shugoshin, provides an additional force holding sister chromatids together. During Anaphase I (i.e. anaphase during the first division), the cohesin is broken, but not the shugoshin, so that the homologous chromosomes but not the sister chromatids are broken apart. During Anaphase II, however, shugoshin is broken down, allowing sister chromatids to end up in the daughter cells.

Appreciate the differences between mitosis & meiosis


Mitosis Meiosis
Number of daughter cells 2 4
Ploidy* of daughter cells Diploid Haploid
Number of cell divisions 1 2
Type of cell divisions Equational Meiosis I: Reductional
Meiosis II: Equational
Crossing over No Yes
Location Many cells of the body Germ cells only

* Ploidy = number of full sets of chromosomes. Diploid (2n) is 46 chromosomes in humans, whereas haploid (n) is 23 chromosomes in humans.

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