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BIO 10 Cell Reproduction Intelligent Design by Owen Borville August 24, 2024

Cell Division and Genomic DNA
The genome is the total genetic information of a cell or organism, including its DNA, packaged as a double-stranded DNA molecule. In prokaryote cells, the genome is composed of a single, double-stranded DNA molecule in the form of a loop or circle. The region in the cell containing this information is called the nucleoid.

In eukaryote cells, the genome consists of several double-stranded linear DNA molecules. Each species of eukaryotes has a characteristic number of chromosomes in the nuclei of its cells.

Human cells have 46 chromosomes, while human gametes (sperm or egg cells) have 23 chromosomes each. A typical body cell contains two equal sets of chromosomes (one from each parent) known as a diploid.

Human cells that contain one set of chromosomes are called gametes or sex cells, egg, sperm, pollen grain, or haploid. The letter n represents a set of chromosomes, so diploids are 2n and haploids are 1n.

During fertilization, each gamete gives one set of chromosomes, which creates a diploid cell with matched pairs of chromosomes (homologous, or same knowledge).  Homologous chromosomes are the same length and have specific nucleotide segments called genes in the exact same location (locus).

Genes, the functional unit of chromosomes, determine specific characteristics by coding for specific proteins. Genes are a sequence of DNA that codes for a protein. Traits are the variations of those characteristics.

The variation of individuals within a species is due to the specific combination of genes (alleles) inherited from both parents. DNA is tightly packed to fit in the cell nucleus, despite measuring two meters in length. The DNA also must be functional while it is packed in the nucleus.

Chromosomes are compacted into the genes of the DNA in several ways:

In the first level of compaction, short stretches of the DNA double-helix structure wrap around a core of eight histone proteins at regular intervals along the entire length of the chromosome. The DNA and chromosome together is called a chromatin.

A nucleosome is a subunit of chromatin composed of a short-length of bead-like DNA wrapped around a core of histone proteins. The DNA connecting the nucleosomes is called  linker DNA. This type of DNA molecule is about seven times shorter than a double-helix structure without the histones, and the beads are 10 nm in diameter, compared to 2 nm for the double helix.

The second level of compaction occurs as the nucleosomes and linker DNA between them coil into a 30 nm chromatin fiber, which is about 50 times shorter than the extended version.

In the third level of compaction, a variety of fibrous proteins is used to pack the chromatin and ensure that each chromosome in a non-dividing cell occupies a particular area of the nucleus that does not overlap with any other chromosome.

DNA replicates in the S phase of interphase, before mitosis. After replication, the chromosomes are comprised of two linked sister chromatids. The pairs of identical chromosomes are bound to each other by cohesion proteins.

The centromere, a highly condensed region, is where the connection between sister chromatids is closest.

The Cell Cycle is an ordered series of events involving cell growth and cell division that produce two new identical daughter cells.

Two Phases of the Cell Cycle: Interphase is when the cell grows and DNA is replicated. The Mitotic phase is when the replicated DNA and cytoplasmic contents are separated, and the cell cytoplasm is usually partitioned by a third process of the cell cycle called cytokinesis.

Interphase is when the cell grows and DNA is replicated. Three stages of interphase are G1, S, and G2.
G1 Phase: (first gap) centered on cell growth during mitosis. Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration.
S Phase: stage during synthesis of DNA replication occurs of identical pairs of DNA molecules (sister chromatids). The centrosome is also duplicated in the S stage. The two centrosomes will spur the mitotic spindle, the organelle that controls the movement of chromosomes during mitosis. Rod-shaped centrioles are positioned at right angles to each other and help organize cell division. G2 Phase: the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation and movement, while some organelles are duplicated, and the cytoskeleton is dismantled. Third phase of interphase where the cell undergoes final preparations for mitosis.

The Mitotic Phase is the period of the cell cycle during which duplicated chromosomes are aligned, duplicated into two nuclei and cytoplasmic contents are divided; includes karyokinesis (or nuclear division) and cytokinesis, the physical separation of cytoplasmic components into the two daughter cells. Karyokinesis (or mitosis) is divided into a series of phases: prophase, prometaphase, metaphase, anaphase, and telophase resulting in the division of the cell nucleus.
The prophase, or first phase, of mitosis during which chromosomes condense and the mitotic spindle begins to form. Condensin proteins help sister chromatids coil during prophase. The prometaphase, or first phase change, is the stage of mitosis when the nuclear membrane breaks down and mitotic spindle fibers attach to kinetochores, which are protein structures associated with the centromere of each sister chromatid that attracts and binds spindle microtubules during prometaphase. Spindle microtubules that do not engage the chromosomes are called polar microtubules. Metaphase or change phase is the stage of mitosis during which chromosomes are aligned at the metaphase plate (equatorial plane) about midway between the two poles of the cell. Anaphase is the upward phase or stage of mitosis during which sister chromatids are separated from each other. Telophase is the distance phase or stage of mitosis where chromosomes arrive at opposite poles, decondense, and are surrounded by a new nuclear envelope.

Cytokinesis or cell motion is the division of cytoplasm following mitosis that forms two daughter cells. The cleavage furrow is the constriction formed by an actin ring during cytokinesis in animal cells that leads to cytoplasmic division. The cell plate is a structure formed during plant cytokinesis by Golgi vesicles, forming a temporary structure (phragmoplast) and fusing at the metaphase plate; this ultimately leads to the formation of cell walls that separate the two daughter cells.
G0 (G zero) Phase is distinct from the G1 phase of interphase because a cell in G0 is not preparing to divide, but rather in a quiescent (or inactive) stage that occurs when cells exit the cell cycle. Quiescent cells are performing normal cell functions and have not prepared for cell division. Some cells enter G0 phase temporarily due to environment conditions, and certain cells stay in G0 permanently, depending on the particular cell's function.

Control of the Cell Cycle
The length of the cell cycle is highly variable, in addition to the length of time in each phase of the cell cycle. External events can trigger the initiation and restriction of cell division, such as the death of nearby cells or growth hormones. Crowding of cells can inhibit division. Cell growth can trigger division.
Cell-cycle checkpoints are mechanisms that monitor the preparedness of a eukaryotic cell to advance through the various cell-cycle stages. Cell cycle progression can be halted until conditions are more favorable. The three cell checkpoints are located at G1, G2, and M.
The G1 checkpoint determines whether all conditions are favorable for cell division to proceed.
The G2 checkpoint blocks entry into the mitotic phase if certain conditions are not met, such as if some chromosomes have not divided of if there is any damage.
The M checkpoint occurs near the end of the metaphase stage of karyokinesis and is known as the spindle checkpoint, checking whether the sister chromatids are correctly attached to the spindle microtubules.
Regulator Molecules of the Cell Cycle: there are two groups of intracellular molecules that regulate the cell cycle by promoting progress (positive) or halting progress (negative).
Positive regulators of the cell cycle include two groups of proteins called cyclins and cyclin-dependent kinases (cdks) that help regulate the cell cycle by phosphorylating key proteins. The concentrations of cyclins vary throughout the cell cycle. The cyclins are also controlled by cytoplasmic enzymes through each stage of the cell cycle.
Cyclins regulate the cell cycle only when they are tightly bound to cdks. Cdks are enzymes or kinases that phosphorylate other proteins.

Negative regulators of the cell cycle stop the cell cycle if there are issues. Examples are retinoblastoma protein (Rb), p53, and p21.
Retinoblastoma proteins are tumor-suppressor proteins common in many cells and bind to transcription factors like E2F. Transcription factors turn on certain genes that produce certain proteins. Rb is slowly phosphorylated until it becomes inactivated. P53 regulates cell growth and monitors DNA damage, stopping the cell cycle if there is damage, can induce apoptosis, or cell death. P21 is a similar protein that is controlled by P53. Positive and negative regulators are turned on and off when needed as the cell moves past each checkpoint in the cell cycle.

Cancer and the Cell Cycle
A common mechanism spurs cancer in cells, and this mechanism is uncontrolled cell growth. Despite the many regulator molecules in the cell cycle, errors still happen. Errors occur in the form of copy errors, or mutations that are passed on to the daughter cells. Mutations can lead to diseases like cancer by creating faulty proteins.
Proto-oncogenes are normal genes that when mutated certain ways become oncogenes, which are genes that cause cells to become cancerous. If oncogenes are allowed to spread, they can be dangerous to the body.
Tumor-suppressor genes are segments of DNA that code for regulator proteins that prevent the cell from undergoing uncontrolled division. Tumor-suppressor gene proteins Rb, p53, and p21 create a roadblock to cell-cycle progression until certain events and functions are completed. A mutated gene may not be able to block the cell cycle if there is an error. Mutated p53 might also be unable to trigger p21 production, which would reduce the ability to regulate the cell cycle and allow the creation and spread of tumors and cancer cells.

Prokaryotic Cell Division
Binary fission is the process of cell division in prokaryotic cells. Binary fission is less complicated and much faster than cell division in eukaryotic cells.
(1) Replication of the circular prokaryotic chromosome begins at the origin of replication and continues in both directions at once. The FtsZ is a tubulin-like protein component of the prokaryotic cytoskeleton that is important in prokaryotic cytokinesis (filamenting temperature-sensitive mutant Z) is a ring of repeating units of protein and directs the partition between nucleoids.
(2) The cell begins to elongate. FtsZ proteins migrate toward the midpoint of the cell.
(3) The duplicated chromosomes separate and continue to move away from each other toward opposite ends of the cell. FtsZ proteins form a ring around the periphery of the midpoint between the chromosomes.
(4) The FtsZ ring directs the formation of a septum that divides the cell. The septum structure forms as a precursor to the separation of the cell into two daughter cells. The plasma membrane and cell wall materials accumulate.
(5) After the septum is complete, the cell pinches in two, forming two daughter cells. FtsZ is dispersed throughout the cytoplasm of the new cells.
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