Human Genetics PDF - Lec 3 and 4 - 3rd Stage

Human Genetics FOLDER No.3 and 4 Department of Medical Laboratory Techniques 3rd Stage Al-Salam University College Baghdad, Iraq Asst.Inst. Omer. S. Ghalib Human Genetics...

Human Genetics FOLDER No.3 and 4 Department of Medical Laboratory Techniques 3rd Stage Al-Salam University College Baghdad, Iraq Asst.Inst. Omer. S. Ghalib Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage Cell cycle checkpoint Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: The G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to- anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein. 1 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage Phases of Cell Cycle A typical eukaryotic cell cycle is illustrated by human cells in culture. These cells divide once in approximately every 24 hours. However, this duration of cell cycle can vary from organism to organism and also from cell type to cell type. Yeast for example, can progress through the cell cycle in only about 90 minutes. The cell cycle is divided into two basic phases: - Interphase (cell growth and copying of chromosomes in preparation for cell division) - Mitotic (M) phase (mitosis and cytokinesis) A) Interphase It represents continuous growth of the cell and is subdivided into three phases, G1 (gap1) phase, S (synthesis) phase and G2 (gap 2) phase. 1- The G1 phase It is usually the longest and the most variable phase of the cell cycle, and it begins at the end of M phase. During the G1 phase, the cell gathers nutrients and synthesizes RNA and proteins necessary for DNA synthesis and chromosome replication. 2- The S phase (DNA replication) Initiation of DNA synthesis marks the beginning of the S phase, which is about 7.5 to 10 hours in duration. The DNA of the cell is doubled during the S phase, and new chromatids are formed. 3- The G2 phase (cell preparation for cell division) During this phase, the cell examines its replicated DNA in preparation for cell division. This is a period of cell growth and reorganization of cytoplasmic 2 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage organelles before entering the mitotic cycle. The G2 phase may be as short as 1 hour in rapidly dividing cells or of nearly indefinite duration in some polypoid cells and in cells such as the primary oocyte that are arrested in G2 for extended periods. B) M Phase (Mitosis phase) Mitosis nearly always includes both karyokinesis (division of the nucleus) and cytokinesis (division of the cell) and lasts about 1 hour. Mitosis takes place in several stages described in more detail below. Separation of two identical daughter cells concludes the M phase. 3 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage Mitosis Cell division is a crucial process that increases the number of cells, permits renewal of cell populations, and allows wound repair. Mitosis is a process of chromosome segregation and nuclear division followed by cell division that produces two daughter cells with the same chromosome number and DNA content as the parent cell. The process of cell division includes division of both the nucleus (karyokinesis) and the cytoplasm (cytokinesis). The process of cytokinesis results in distribution of nonnuclear organelles into two daughter cells. Before entering mitosis, cells duplicate their DNA in the S or synthesis phase. Phases of Mitosis 1. Prophase: The replicated chromatin condenses and become visible as chromosomes. Each chromosome can be seen to consist of two chromatids. The sister chromatids are held together by the ring of proteins at the centromere. In late prophase, the nuclear envelope begins to disintegrate, and the nucleolus completely disappears. In addition, a highly specialized protein complex called a kinetochore appears on each chromatid opposite to the centromere. 2. Metaphase: Formation of the mitotic spindle, consisting of three types of microtubules, that becomes organized around the centrosomes, the astral microtubules, the polar microtubules and the kinetochore microtubules. When a kinetochore is finally captured by a kinetochore microtubule, it is pulled toward the centrosomes, Kinetochore microtubules and their associated motor proteins direct the 4 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage movement of the chromosomes to a plane in the middle of the cell, called the equatorial or metaphase plate. 3. Anaphase: Separation of sister chromatids. This separation occurs when the proteins that have been holding the chromatids together break down. The separated chromatids are pulled to opposite poles of the cell by the sliding along the kinetochore microtubules toward the centrosomes. 4. Telophase: Reconstitution of a nuclear envelope around the chromosomes at each pole. The chromosomes uncoil and become indistinct. The nucleoli reappear, and the cytoplasm divides (cytokinesis) to form two daughter cells. Cytokinesis Cytokinesis begins with the furrowing of the plasma membrane midway between the poles of the mitotic spindle. The separation at the cleavage furrow is achieved by a contractile ring consisting of a very thin array of actin filaments positioned around the perimeter of the cell. As the ring tightens, the cell is pinched into two daughter cells. Because the chromosomes in the daughter cells contain identical copies of the duplicated DNA, the daughter cells are genetically identical and contain the same kind and number of chromosomes. The daughter cells are (2d) in DNA content and (2n) in chromosome number. 5 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage Meiosis Meiosis involves two sequential nuclear divisions followed by cell divisions that produce gametes (sex cells) containing half the number of chromosomes and half the DNA found in somatic cells. -The zygote (the cell resulting from the fusion of an ovum and a sperm) and all the somatic cells derived from it are diploid (2n) in chromosome number (46 chromosomes in human); thus, their cells have two copies of every chromosome and every gene encoded on this chromosome. 6 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage -These chromosomes are called homologous chromosomes because they are similar but not identical; one set of chromosomes is of maternal origin, the other is from paternal origin. - The gametes, having only one member of each chromosome pair, are described as haploid (1n). - During gametogenesis, reduction in chromosome number to the haploid state (23 chromosomes in humans) occurs through meiosis. - This reduction is necessary to maintain a constant number of chromosomes in a given species. - Reduction in chromosome number to (1n) in the first meiotic division is followed by reduction in DNA content to the haploid (1d) amount in the second meiotic division. - During meiosis, the chromosome pair may exchange chromosome segments, thus altering the genetic composition of the chromosomes. This genetic exchange, called crossing-over, and the random assortment of each member of the chromosome pairs into haploid gametes give rise to infinite genetic diversity. Differences in Meiosis between Male & Female The nuclear events of meiosis are the same in males and females, but the cytoplasmic events are markedly different. In males, the two meiotic divisions of a primary spermatocyte yield four structurally identical, although genetically unique, haploid spermatids. Each spermatid has the capacity to differentiate into a spermatozoon. In contrast, in females, the two meiotic divisions of a primary oocyte yield one haploid ovum and three haploid polar bodies. The ovum receives most of the 7 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage cytoplasm and becomes the functional gamete. The polar bodies receive very little cytoplasm and degenerate. Divisions & Phases of Meiosis Meiosis consists of two successive mitotic divisions without the additional S phase between the two divisions. During the S phase that precedes meiosis, DNA is replicated forming sister chromatids (two parallel strands of DNA) joined together by the centromere. The DNA content becomes (4d), but the chromosome number remains the same (2n). The cells then undergo a reductional division (meiosis I) and an equatorial division (meiosis II). During meiosis I, as the name reductional division implies, the chromosome number is reduced from diploid (2n) to haploid (1n), and the amount of DNA is reduced from the (4d) to (2d). No DNA replication precedes meiosis II. The division during meiosis II is always equatorial because the number of chromosomes does not change. It remains at (1n), although the amount of DNA represented by the number of chromatids is reduced to (1d). Phases of Meiosis I 1. Prophase I: It is an extended phase that is subdivided into the following five stages: Leptotene: chromosomes start to condense. Zygotene: homologous chromosomes become closely associated (synapsis) to form pairs of chromosomes (bivalents) consisting of four chromatids (tetrads). 8 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage Pachytene: crossing over between pairs of homologous chromosomes to form chiasmata (sing. chiasma). Diplotene: homologous chromosomes start to separate but remain attached by chiasmata. Diakinesis: homologous chromosomes continue to separate, and chiasmata move to the ends of the chromosomes. 2. Metaphase I: Metaphase I is similar to the metaphase of mitosis except that the paired chromosomes are aligned at the equatorial plate with one member on either side. - The chiasmata are cut, and the homologous chromosomes separate completely. - The spindle microtubules begin to interact with the chromosomes through the kinetochore at the centromere. - The chromosomes undergo movement to ultimately align their centromeres along the equatorial plate with one member of the homologous chromosomes on either side. 3. Anaphase I: The sister chromatids, held together by protein complexes and by the centromere, remain together. - A maternal or paternal member of each homologous pair moves to each pole. - Segregation or random assortment occurs because the maternal and paternal chromosomes of each pair are randomly aligned on one side or the other of the metaphase plate, thus contributing to genetic diversity. 9 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage 4.Telophase I: - Homologous chromosomes, each consisting of two sister chromatids, are at the opposite poles of the cell. - Reappearance of the nucleolus and nuclear envelope. - At the completion of meiosis I, the cytoplasm divides. Each resulting daughter cell is haploid in chromosome number (1n) and contains one member of each homologous chromosome pair. The cell is still diploid in DNA content (2d). Phases of Meiosis II: After meiosis I, the cells quickly enter meiosis II without passing through an S phase. - Meiosis II is an equatorial division and resembles mitosis. - During this phase, the sister chromatids will separate at anaphase II and move to opposite poles of the cell. - During meiosis II, the cells pass through prophase II, metaphase II, anaphase II, and telophase II. - These stages are essentially the same as those in mitosis except that they involve a haploid set of chromosomes (1n) and produce daughter cells that have only haploid DNA content (1d). - Unlike the cells produced by mitosis, which are genetically identical to the parent cell, the cells produced by meiosis are genetically unique. 10 Human Genetics Asst.Inst. Omer S. Ghalib Lec: 3 and 4 3rd stage By the end of meiosis II, each parent cell (2n) give rise to 4 daughter cells with haploid number of chromosomes (In) and each daughter cell is genetically different from the parent cell 11