Mitosis describes the division of one cell into two identical daughter cells. It occurs in several stages, each of which consists of a stereotyped set of changes in cell contents and structure. In this article, we will look at the stages of mitosis and its clinical relevance.
Stages of Mitosis
Each chromosome is made of two genetically identical chromatids, joined by a centromere. During DNA replication, genetic material is loosely packed as chromatin. However, during mitosis DNA needs to be more tightly packed to allow for easier separation in anaphase. At the start of prophase, chromatin begins condensing into chromosomes.
In addition, mitotic spindles begin to form. Mitotic spindles are structures made from microtubules that aid in the organisation and arrangement of chromosomes. The spindles attach to an organelle known as the centrosome. Each cell in mitosis has two centrosomes; during prophase, the centrosomes begin to move in opposite directions.
In this stage the chromosomes finish condensing into their compact state. The nuclear envelope begins to breakdown, allowing spindle fibres to attach to the chromosomes at a site called the kinetochore (an area of the centromere found on each sister chromatid). The sister chromatids are attached to spindles that originate from the opposite centrosome, linking the two together.
At this stage, the chromosomes align upon a theoretical line known as the metaphase plate. The centrosomes have finished moving and are located at opposite ends of the cell.
At this stage, the cell will check that all the chromosomes are aligned along the metaphase plate, with their kinetochores correctly attached. This helps to ensure sister chromatids are split evenly between the two daughter cells. An error in chromosomal alignment or spindle attachment will result in the cell halting further progress until the problem is fixed.
During this stage, sister chromatids are pulled to opposite ends of the cell. The spindle fibres contract, breaking the chromatids at the centromere and moving them to opposite poles of the cell. Spindle fibres not attached to chromatids will elongate the cell to prepare it for division.
In this phase the cell has elongated and is nearly finished dividing. Cell-like features begin to reappear such as reformation of two nuclei (one for each cell). The chromosomes decondense and the mitotic spindles fibres are broken down.
Cytokinesis is the division of the cytoplasm to form two new cells. This stage actually begins between anaphase and telophase, however doesn’t finish until after telophase. To separate the two cells, a ring of protein (actin ring) pinches the cytoplasm along a crease known as a cleavage furrow. This splits the cytoplasm equally between the two cells.
Clinical Relevance – Errors of Mitosis
Errors in mitosis usually occur during metaphase. Usually this is due to misalignment of chromosomes along the metaphase plate or a failure of the mitotic spindles to attach to one of the kinetochores. This can result in the daughter cells having unequal distribution of chromosomes, leaving one cell with one too many and the other with one too few.
The cell missing a chromosome usually dies, however the cell with the extra chromosome can cause problems. If the extra chromosome carries genes that promote cell growth, this may lead to cancer via constitutive activation of signalling pathways within the cell. However, it is important to note the mechanism of cancer is complex and requires several genetic ‘hits’; the addition of an extra chromosome on its own would be insufficient to cause cancer.