Topic 5: Mitotic cell cycle
5.1 Replication and division of nuclei and cells
Students should be able to:
1) describe the structure of a chromosome
2) explain the importance of mitosis in the production of genetically identical daughter cells
3) outline the mitotic cell cycle
4) outline the role of telomeres in preventing the loss of genes from the ends of chromosomes during DNA replication
5) outline the role of stem cells in cell replacement and tissue repair by mitosis
6) explain how uncontrolled cell division can result in the formation of a tumour
1 — Structure of a chromosome (DNA, histone proteins, sister chromatids, centromere, telomeres)
A chromosome is a DNA-based structure in which a long double-helical DNA molecule is associated with histone proteins that package the DNA by forming nucleosomes and higher-order coils so that the very long DNA fits into the nucleus; when a chromosome has been replicated it consists of two identical DNA molecules called sister chromatids, each chromatid being one DNA duplex packaged with histones, and these sister chromatids are joined at a specialised constricted region called the centromere which is essential for attachment of spindle microtubules and correct segregation during mitosis; the ends of linear chromosomes are capped by telomeres, short repeated DNA sequences and associated proteins that protect chromosome ends from degradation and from being recognised as DNA breaks, and which prevent loss of coding DNA during successive rounds of replication by providing a buffer of repeat sequence.
2 — Importance of mitosis in producing genetically identical daughter cells (growth, replacement, repair, asexual reproduction)
Mitosis produces two genetically identical daughter nuclei by accurately segregating one copy of each replicated chromosome to each daughter cell, and this precise duplication and partitioning of genetic material underpins multicellular growth (where tissues expand by increasing cell number), replacement of damaged or dead cells (so lost cells are restored without altering the organism’s genetic information), repair of tissues by cell replacement (for example skin and gut epithelia), and forms the basis of many types of asexual reproduction where offspring are genetically identical to the parent because mitotic divisions, rather than meiotic divisions, generate the new body or propagule.
3 — Outline of the mitotic cell cycle (interphase: G1, S, G2; mitosis; cytokinesis)
The mitotic cell cycle consists of an interphase during which the cell grows and prepares for division followed by mitosis and cytokinesis: in G1 the cell increases in size, synthesises proteins and organelles and carries out its specialised functions; in S phase the nuclear DNA is precisely replicated so each chromosome becomes two sister chromatids; in G2 the cell continues to grow and synthesises microtubules and other proteins needed for mitosis and checks for DNA replication errors; during mitosis (prophase, metaphase, anaphase, telophase) the replicated chromosomes condense, attach to spindle microtubules and are segregated to opposite poles, and finally cytokinesis physically divides the cytoplasm to produce two separate daughter cells—together these stages ensure accurate replication and equal partitioning of genetic and cellular components.
4 — Role of telomeres in preventing loss of genes from chromosome ends during DNA replication
Telomeres are repetitive non-coding DNA sequences at the ends of linear chromosomes that provide a protective buffer so that the inevitable shortening that occurs during DNA replication (the end-replication problem) removes repeats rather than functional genes; telomeric repeat DNA and associated proteins also form specialised structures that protect chromosome ends from exonuclease digestion and from inappropriate DNA repair, and in some cell types the enzyme telomerase can extend telomeres to maintain their length, thereby preserving genomic integrity through many cell divisions.
5 — Role of stem cells in cell replacement and tissue repair by mitosis
Stem cells are populations of relatively undifferentiated cells that can both self-renew by mitotic division to maintain the stem cell pool and differentiate into specialised cell types required for tissue maintenance and repair, and because they can proliferate and produce daughter cells that enter differentiation pathways, stem cells act as a continual source of new cells to replace damaged or aged cells in tissues such as blood, skin and gut, enabling regeneration and repair while preserving genetic identity by mitotic divisions.
6 — How uncontrolled cell division can result in tumour formation
Uncontrolled cell division arises when normal regulatory mechanisms that govern cell cycle progression, DNA repair and apoptosis are disrupted—often by mutations in genes that regulate the cell cycle (such as proto-oncogenes that become oncogenes or tumour suppressor genes that lose function)—leading to excessive, uncoordinated proliferation of cells; the result is a mass of cells called a tumour, and if regulatory loss also allows invasion of neighbouring tissues and dissemination to distant sites the tumour is malignant (cancer), whereas tumours that remain local and do not invade are described as benign.
5.2 Chromosome behaviour in mitosis
Students should be able to:
1) describe the behaviour of chromosomes in plant and animal cells during the mitotic cell cycle and the associated behaviour of the nuclear envelope, the cell surface membrane and the spindle (names of the main stages of mitosis are expected: prophase, metaphase, anaphase and telophase)
2) interpret photomicrographs, diagrams and microscope slides of cells in different stages of the mitotic cell cycle and identify the main stages of mitosis
1) Behavior of chromosomes, nuclear envelope, cell surface membrane and spindle during mitotic stages (prophase, metaphase, anaphase, telophase)
During prophase chromosomes condense into visible structures as sister chromatids become shorter and thicker, the nucleolus fades, the nuclear envelope begins to break down, and the mitotic spindle starts to form from microtubule organising centres (centrosomes with centrioles in animal cells) that move to opposite poles; in prometaphase (part of late prophase in some schemes) spindle microtubules attach at the centromeres; in metaphase chromosomes are aligned at the cell equator (the metaphase plate) with sister kinetochores attached to microtubules from opposite poles; in anaphase the centromeric cohesion between sister chromatids is released so chromatids separate and are pulled as individual chromosomes toward opposite poles by shortening kinetochore microtubules and by spindle pole separation; during telophase chromosomes arrive at poles and begin to decondense, the nuclear envelope re-forms around each set of chromosomes and the nucleolus reappears while the spindle disassembles; concurrently cytokinesis partitions the cytoplasm—by cleavage furrow formation driven by an actin-myosin contractile ring in animal cells, or by assembly of a new cell plate from Golgi-derived vesicles that develop into a new cell wall in plant cells—so that two daughter cells with intact nuclei and membranes are produced.
2) Interpreting photomicrographs, diagrams and slides of cells in different stages of the mitotic cell cycle and identifying main stages of mitosis
Identification of mitotic stages in micrographs relies on characteristic features: prophase shows condensed chromosomes in a nucleus with a fading nucleolus and little or no nuclear envelope; metaphase shows chromosomes aligned centrally as discrete X-shaped structures with centromeres on the metaphase plate; anaphase is recognised by the separation and movement of chromatids (now individual chromosomes) toward opposite poles, producing a V- or U-shaped appearance for moving chromosomes; telophase and early interphase show decondensing chromosomes, the re-formation of nuclear envelopes and nucleoli, and evidence of cytokinesis such as a cleavage furrow or developing cell plate; distinguishing plant from animal cells uses clues such as the presence of a cell plate or rigid cell wall in plants and clear centrosomes/cleavage furrows in many animal cells, and careful observation of chromosome condensation, spindle microtubules (if visible), nuclear membrane integrity and cytoplasmic partitioning allows accurate assignment of the stage.