Cell Division, Chromosomes, and Cell Cycle

• Cell division primarily results in genetically identical daughter cells
• During the cell cycle, the mitotic phase alternates with interphase
• The eukaryotic cell cycle is controlled by a molecular system
• Meiosis is a specialized type of cell division that reduces the number of chromosome sets from diploid to haploid

Understanding the Cell Cycle

• Cell division is essential for the continuity of life and is known as the cell cycle
• Cell division in unicellular organisms reproduces the entire organism
• Multicellular organisms rely on cell division for growth, development, and repair.
• Most cell divisions produce daughter cells with identical genetic information to the parent cell (DNA)
• Meiosis is an exception, producing sperm and egg cells

Chromosomes Explained

• DNA is organized and packaged into chromosomes
• Chromatin, a DNA and protein complex, condenses to form chromosomes during cell division
• Every eukaryotic species is characterized by a specific number of chromosomes
• Human somatic (non-reproductive) cells contain two sets of chromosomes, totaling 46 (2 × 23)
• Gametes (sperm and egg cells) contain half the number of chromosomes found in somatic cells

Sister Chromatids

• DNA replicates and chromosomes condense in preparation for cell division
• A duplicated chromosome consists of two sister chromatids, which are copies of the original chromosome, joined by cohesin proteins
• The centromere represents the constriction point on a duplicated chromosome where sister chromatids are most closely attached
• Sister chromatids separate during cell division and move into two separate nuclei

Interphase & Mitotic Phases

• Eukaryotic cell cycle consists of interphase and the Mitotic (M) phase
• Interphase accounts for about 90% of the cell cycle
• Interphase can be divided into G1 phase ("first gap"), S phase ("synthesis"), and G2 phase ("second gap")
• Cell grows during all three subphases; chromosomes are duplicated only during S phase
• The Mitotic (M) phase involves mitosis (division of chromosomes) and cytokinesis (division of cytoplasm)

Mitosis Phases

• Mitosis is divided into five phases: prophase, prometaphase, metaphase, anaphase, and telophase
• Cytokinesis overlaps with the later stages of mitosis
• In prophase, chromatin condenses into chromosomes, and the mitotic spindle begins to form
• During prometaphase, the nuclear envelope fragments, and a kinetochore forms at the centromere of each chromatid; microtubules from the mitotic spindle attach to kinetochores
• Centrosomes are at opposite poles of the cell during metaphase, and chromosomes align at the metaphase plate; kinetochores attach to microtubules on opposite poles
• Anaphase is the shortest stage; cohesin proteins are cleaved, and sister chromatids separate, with complete sets of chromosomes at opposite ends of the cell by the end
• Telophase sees two daughter nuclei form, chromosomes become less condensed, and cytokinesis occurs, dividing the cell in two

Mitotic Spindle

• The mitotic spindle, made of microtubules, is responsible for chromosome movement during mitosis
• Spindle microtubules' assembly begins in the centrosome in animal cells
• The centrosome replicates during interphase, with the two resulting centrosomes migrating to opposite ends during prophase and prometaphase
• Aster (radial array of short microtubules) extends from each centrosome
• The spindle includes the centrosomes, spindle microtubules, and asters

Kinetochores

• During prometaphase, spindle microtubules attach to kinetochores and initiate chromosome movement; these are called kinetochore microtubules
• Kinetochores are protein complexes forming in association with chromosome centromeres

Metaphase Plate

• During metaphase, chromosomes align at the metaphase plate, which is the midpoint between the two spindle poles

Separating Sister Chromatids

• Sister chromatids separate and move along kinetochore microtubules toward spindle poles during anaphase
• Microtubules retract through depolymerization at their their kinetochore ends
• Nonkinetochore microtubules from opposite poles overlap; they elongate and push against each other to elongate cell and move spindle poles apart
• Separation of daughter chromosomes during process is thereby facilitated

M Phase Completion

• Genetically identically daughter nuclei form at opposite cell ends in telophase
• Anaphase or telophase marks the beginning of cytokinesis

Cytokinesis

• Animal cell cytokinesis occurs through cleavage, creating cleavage furrow via actin microfilaments.
• Plant cells form a cell plate during cytokinesis

Binary Fission

• Prokaryotes (bacteria and archaea) reproduce through binary fission
• During binary fission, the chromosome replicates (starting at the origin of replication), and two daughter chromosomes separate
• Plasma membrane pinches inward, splitting the cell into two
• Mitosis probably evolved from binary fission, as prokaryotes predated eukaryotes
• Mitochondria and chloroplasts divide independently within eukaryotic cells via binary fission
• Some protists exhibit cell division methods that appear as a cross between binary fission and mitosis

Cell Cycle Checkpoints

• A specific cell cycle control system directs cell cycle events in sequence, analogous to a clock
• This clock is controlled by internal and external signals
• The cell cycle halts at specific checkpoints until a go-ahead signal is received
• The G1, G2, and M checkpoints are among the most crucial and best understood

G1 Checkpoint & G0 phase

• G1 checkpoint is very important for many cells
• The cell usually completes the S, G2, and M phases and divides upon receiving a "go-ahead" signal at G1
• If the go-ahead signal is not received, the cell exits the cell cycle and enters the non-dividing G0 phase
• Nutrient availability or differentiation status commonly regulate the G1 checkpoint (ex. terminally differentiated neurons)

G2 Checkpoint

• Cyclins and cyclin-dependent protein kinases are the two regulatory proteins involved in cell cycle regulation (Cdks)
• Cdks are controlled by cyclins and cycle concentrations, and activity cycles in turn
• Cyclin-Cdk complex (maturation-promoting factor) triggers a cell's movement past the G2 checkpoint into M phase

M Checkpoint

• Cells do not proceed past the M checkpoint to anaphase until all chromosomes are correctly linked to spindle microtubules at respective kinetochores
• Ensures appropriate chromosome number distribution to daughter cells
• Anaphase is delayed by an intracellular or extracellular signal, with anaphase inhibited until complete chromosome attachment to spindle fibres
• Some external signals, like growth factors (proteins secreted by particular cells), stimulate other cells to distribute in this way

Growth Factors

• Growth factors include external influences on cell proliferation
• Secrete certain signalling cells to stimulate cell division in other cell types
• Platelet-derived growth factor (PDGF), derived from blood cell fragments such as platelets, stimulates additional cells to divide.

When Division is Halted

• Animal cells exhibit anchorage dependence and need to be affixed to a substrate to divide
• Density-dependent inhibition is an additional external factor, in which congested cells halt division
• Cancer cells do not display density-dependent inhibition or are anchorage dependent
• Growth factors and their existence is where cancer cells may differ:
  • Cancer cells may produce their own growth factors
  • Cancer cells may transmit growth factor signals, even without the presence of their stimuli
  • Cancer cells may not be subject to typical cell cycle limitations

Transformation

• Transformation is the process by which a normal cell converts to a cancerous cell
• Cancer cells that immune system does not eliminate develops tumors, abnormal cell masses within otherwise normal cells
• Benign tumor is the state when abnormal cells remain in the initial site.
• Malignant tumors are those that spread throughout the body into surrounding tissues via metastasis, where additional tumors form.

Life Cycle

• A life cycle covers the generational phases of the reproductive history of an organism
• Fertilization and meiosis cycle with each other in sexual reproduction to sustain chromosome number
• Zygote are referred to as fertilized eggs, and they possess single chromosome of each parent
• Somatic cells are generated by the mitosis of the zygote at the time of its development as it matures into adult
• During sexual maturity, ovaries and testes give rise to haploid gametes
• Meiosis creates animal types of human cells
• The gamete only consists of one chromosome inside per meiotic event.

Alternation of Generations

• Fertilization and alternation of meiosis is common to all sexually producing beings
• Three sex life cycles (animals, plants, fungi) vary in time to allow meiosis and fertilization
• Mitosis may be used in either haploid or diploid cells, as determined by each life
• Remember that only diploid may undergo meiosis.

Meiosis Overview

• Chromosome replication is a precursor to both mitosis and meiosis
• Meiosis entails undergoing two rounds of division; it comprises of meiosis I and II, where two sets of cell divisions give rise to four daughter cells
  • Meiosis I (reductional division): homologous chromosomes separate from one another
  • Meiosis II (equational division): sister chromatids separate from one another
• As such, four daughter cells with unreplicated chromosomes are the resulting product from the above phases

Meiosis phase I

• Four phases make up cell division during meiosis
• Non-chromosome replication takes place with both ends of and start of meiosis phases I and II because of previously replicated chromosomes

Prophase I

• Homologous pairs loosely converge together to form tetrads
• Homologous chromosomes are synapsed through this process
• Homologous chromosomes connect together with a protein complex known as the synaptonemal complex
• Nonsister chromatids share the same genetics through crossover that occurs with synapsis
• As crossing over happens, chiasma (chiasmata pl.) can emerge; this cross over is between nonsister chromatids.

Recombinant Chromosomes

• Recombinant chromosomes are a product when crossing over, combining one DNA from each parent
• One to three average events for crossover can occur for each chromosome in humans
• Genetic variety is obtained through the mixing of genes by crossing over

Principle of Independent Assortment

• Chromosome homologue pairs are randomly oriented in the phase of metaphase I
• The homologue pairings classify its maternal genes, and those homologs with paternal relations, to daughter cells in an independent behavior
• Gamete assortment reaches up to 2^n (n represents 23 haploids and the total comes to 8 million 2^23) combinations of genetic chromosomes for possible inheritance in humans

Meiosis phase II

• With four phases occurring in the division of meiosis II, this replicates what occurs in mitosis
• During the completion of meiosis, there are a total of four daughter cells; genetic uniqueness marks how the arrangement of haploidy contrasts as distinct with those of the ones existing in parent cell.

Mitosis vs. Meiosis

• Mitosis helps conserve chromosome pairs to give rise to parent cell's genetic identity with cells that produce the pairs
• Contrastingly, in meiosis for what occurs in cellular reproduction through genetic distinctness, there is a removal of chromosome numbers in a pair that leads to only haploid sets, diverging in terms of genetic identity from one another, where a new parent cell exists

Explore cell division reasons, chromosome differences between somatic cells and gametes. Learn about DNA replication, cohesin proteins, chromatin, and key cell cycle phases. Understand checkpoints, growth factors, PDGF, anchorage dependence, and density-dependent inhibition.