Cell Cycle & Mitosis (PDF)

3-THE CELL CYCLE & MITOSIS A human, as well as every sexually reproducing organism, begins life as a fertilized egg or zygote. Trillions of cell divisions subsequently occur in a controlled manner to produce a complex, multicellular human. Single-celled organisms use cell division as their method of...

3-THE CELL CYCLE & MITOSIS A human, as well as every sexually reproducing organism, begins life as a fertilized egg or zygote. Trillions of cell divisions subsequently occur in a controlled manner to produce a complex, multicellular human. Single-celled organisms use cell division as their method of reproduction. 1.1 DNA Organization and the Cell Cycle The cell cycle is an orderly sequence of events that describes the stages of a cell’s life from the division of a single parent cell to the production of two genetically identical new daughter cells. The mechanisms involved in the cell cycle are highly regulated. 1.1.1 Genomic DNA Before discussing the steps a cell must undertake to replicate, we need a deeper understanding of the structure and function of a cell’s genetic information. A cell’s DNA, packaged as double-stranded DNA molecules, is called its genome. In prokaryotes, the genome is composed of a single circular double-stranded DNA molecule. The region in the cell containing this genetic material is called a nucleoid. Some prokaryotes also have smaller loops of non- essential DNA called plasmids. Bacteria can exchange these plasmids with other bacteria, sometimes receiving beneficial new genes that the recipient can add to their chromosomal DNA. Antibiotic resistance is one trait that often spreads through a bacterial colony through plasmid exchange. In eukaryotic cells, the genome consists of several double-stranded linear DNA molecules. Each species has a characteristic number of chromosomes in the nuclei of its cells. Human body cells have 46 chromosomes, while human gametes (sperm or eggs) have 23 chromosomes each. A typical body cell, or somatic cell, contains two matched sets of chromosomes, a configuration known as diploid. The letter n is used to represent a single set of chromosomes; therefore, a diploid organism is designated 2n. 41 Human cells that contain one set of chromosomes are called gametes, or sex cells; these are eggs and sperm, and are designated 1n, or haploid. Matched pairs of chromosomes in a diploid organism are called homologous (“same knowledge”) chromosomes. Homologous chromosomes are the same length and have specific nucleotide segments called genes in exactly the same location, or locus. Genes are the functional units of chromosomes and determine specific characteristics by coding for specific proteins. Traits are the variations of those characteristics. For example, hair color is a characteristic with traits that are blonde, brown, or black. Each copy of a homologous pair of chromosomes originates from a different parent; therefore, the genes themselves are not identical. The variation of individuals within a species is due to the specific combination of the genes inherited from both parents. Even a slightly altered sequence of nucleotides within a gene can result in an alternative trait. A karyotype of human chromosomes, showing their distinct sizes and banding patterns. In this image, the chromosomes were exposed to fluorescent stains to highlight chromosomes in different colors. 42  1.1.2 Eukaryotic Chromosomal Structure and Compaction If the DNA from all 46 chromosomes in a human cell nucleus was laid out end to end, it would measure approximately two meters; however, its diameter would be only 2 nm. Considering that the size of a typical human cell is about 10 µm (100,000 cells lined up to equal one meter), DNA must be tightly packaged to fit in the cell’s nucleus. At the same time, it must also be readily accessible for the genes to be expressed. During some stages of the cell cycle, the long strands of DNA are condensed into compact chromosomes. There are a number of ways that chromosomes are compacted. 43 DNA replicates in the S phase of interphase. After replication, the chromosomes are composed of two linked sister chromatids. When fully compact, the pairs of identically packed chromosomes are bound to each other by cohesin proteins. The connection between the sister chromatids is closest in a region called the centromere. The conjoined sister chromatids, with a diameter of about 1 µm, are visible under a light microscope. The centromeric region is highly condensed and thus will appear as a constricted area. 44  1.2 | The Cell Cycle The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Somatic cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two genetically identical cells. In other words, a typical 2n somatic cell will divide into two 2n somatic cells that are genetically identical. This is a form of asexual reproduction. we see two major phases: interphase and the M phase. During interphase, the cell undergoes three distinct periods: G1, S, and G2. During G1, S, and G2, the cell grows, DNA is replicated, and the cell grows some more. During the M phase, the cell undergoes two distinct periods: mitosis (also called karyokinesis) and cytokinesis, the division of the cytoplasm. Figure: cell cycle 45 1.2.1 Interphase During interphase, the cell undergoes normal growth processes while also preparing for cell division. In order for a cell to move from interphase into the mitotic phase, many internal and external conditions must be met. The three aspects or stages of interphase are called G1, S, and G2. G1 Phase (First Gap) The first stage of interphase is called the G1 phase (first gap) because, from a microscopic aspect, little change is visible. However, during the G1 stage, the cell is quite active at the biochemical level. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins as well as accumulating sufficient energy reserves to complete the task of replicating each chromosome in the nucleus. S Phase (Synthesis of DNA) Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase, DNA replication can proceed to form identical pairs of DNA molecules—sister chromatids—that are firmly attached to the centromeric region. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi. G2 Phase (Second Gap) In the G2 phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G2. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis. 46  1.2.2 The Mitotic Phase The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved into two new, identical daughter cells. M phase is divided into mitosis and cytokinesis. Mitosis Mitosis is divided into a series of phases—Prophase, Prometaphase, Metaphase, Anaphase, and Telophase—that result in the division of the cell nucleus. 47 48 Cytokinesis Cytokinesis, or “cell motion,” is the second main stage of the mitotic phase during which cell division is completed via the physical separation of the cytoplasmic components into two daughter cells. Division is not complete until the cell components have been apportioned and completely separated into the two daughter cells. Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells. In cells such as animal cells that lack cell walls, cytokinesis actually begins at the midpoint of Anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former Metaphase plate. The actin filaments pull the equator of the cell inward, forming a constriction. This constriction or fissure is called the cleavage furrow. The furrow deepens as the actin ring contracts, and eventually the membrane is cleaved in two. In plant cells, a new cell wall must form between the daughter cells. During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking into vesicles and dispersing throughout the dividing cell. During telophase, these Golgi vesicles are transported on microtubules to form a phragmoplast (a vesicular structure) at the metaphase plate. There, the vesicles fuse and coalesce from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell walls at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall made of cellulose. Remember that cellulose is a structural polymer of glucose. The Golgi membranes become parts of the plasma membrane on either side of the new cell wall. 49  1.2.3 G0 Phase (A variation of the cell cycle) Not all cells adhere to the classic cell cycle pattern in which a newly formed daughter cell immediately enters the preparatory phases of interphase, closely followed by the mitotic phase. Cells in G0 phase (“G zero”) are not actively preparing to divide. The cell is in a quiescent (inactive) stage that occurs when cells exit the cell cycle. Some cells enter G0 temporarily until an external signal triggers the onset of G1. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G0 permanently. Although cells in G0 are inactive in the sense that they are not actively preparing for and undergoing cell division, they can be very active in other ways. Many cells in the adult body for instance, are permanently in G0 while fulfilling their specialized functions. 50  1.3.2 Regulation of the Cell Cycle at Internal Checkpoints It is essential that the daughter cells that have been produced be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. To prevent a compromised cell from continuing to divide, there are internal control mechanisms that operate at three main cell cycle checkpoints. A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable. These checkpoints occur: 1. near the end of G1, 2. at the G2/M transition, and 3. during metaphase. 1- The G1 Checkpoint The G1 checkpoint determines whether all conditions are favorable for cell division to proceed. The G1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. External influences, such as growth factors, play a large role in carrying the cell past the G1 checkpoint. In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G1 checkpoint. A cell that does not meet all the requirements will not be allowed to progress into the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G0 and await further signals when conditions improve. 2- The G2 Checkpoint The G2 checkpoint bars entry into the mitotic phase if certain conditions are not met. 51  As at the G1 checkpoint, cell size and protein reserves are assessed. However, the most important role of the G2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA. 3- The M Checkpoint The M checkpoint occurs near the end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle checkpoint, because it determines whether all of the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell. 52