Cell Division and Cell Cycle PDF

CELL DIVISION AND CELL CYCLE By SAISHA  INTRODUCTION Before differentiation, most cells undergo repeated cycles of macromolecular synthesis (growth) and division (mitosis). The regular sequence of events that result in new cells is termed the cell cycle. I...

CELL DIVISION AND CELL CYCLE By SAISHA  INTRODUCTION Before differentiation, most cells undergo repeated cycles of macromolecular synthesis (growth) and division (mitosis). The regular sequence of events that result in new cells is termed the cell cycle. Improved knowledge about how each phase  INTRODUCTION of the cell cycle is controlled and how the quality of molecular synthesis, particularly DNA replication, is monitored has led to understanding the causes of many types of cancer, in which cells proliferate without those controls  CELL CYCLE Is period from the birth of the cell to the time it divides into two daughter cells is the period of time between the birth of a cell and its own division to produce two daughter cells It lasts a minimum of 12 hours, but in most adult tissues is considerably longer, s divided into four distinct phases, which are known as G1, S, G2 and M  CELL CYCLE G1 is the period when cells respond to growth factors Cells that retain the directing the cell to initiate capacity for another cycle; once made, this decision is proliferation, irreversible. It is also the phase in which but which are no longer most of the molecular dividing, have entered a machinery required to phase called G0 and are complete another cell cycle is generated. E.g RNA synthesis described as quiescent and proteins that control cell Growth factors can cycle progression stimulate quiescent cells to Increase in cell size leave G0 and re-enter the cell cycle  DNA replication occurs The times taken for S, G2 during S phase, at the end and M are similar for of which the DNA content most cell types, and of the cell has doubled. occupy : 6-8, 2-4 and 1-2 During G2, the cell hours respectively. prepares for division; In contrast, the duration this period ends with the of G1 shows considerable breakdown of the variation, nuclear membrane and sometimes ranging from the onset of less than 2 hours in chromosome rapidly dividing cells, to condensation. more than 100 hours within the same tissue.  Check points At the G1-S and G2-M transitions, members of a family of proteins called cyclins attain their maximum abundance in the cell. The G1 cyclins progressively accumulate during G1. The M phase cyclins accumulate during late S phase and throughout G2. High concentrations of cyclin proteins activate a family of cyclin-dependent protein kinase enzymes (CDKs), which are present in constant concentrations during the cell cycle, although their state of activation varies. The activation of different cyclin-CDK complexes regulates the G1-S and G2- M transitions  MITOSIS AND MEIOSIS Mitosis occurs in most Moreover, meiosis includes a phase in which exchange of somatic cells. genetic material occurs It results in the distribution between homologous chromosomes. of identical copies of the This allows a reassortment of parent cell genome to the genes to take place, which means that the daughter cells two daughter cells. differ from the parental cell in In meiosis, the divisions both their precise genetic sequence and their haploid immediately before the state. final production of gametes In meiosis, two divisions occur halve the number of in quick succession. chromosomes to the Meiosis I is unlike mitosis, whereas meiosis II is more like haploid number, mitosis so that at fertilization the  MITOSIS New DNA is synthesized during the S phase of the cell cycle interphase. This means that the amount of DNA in diploid cells has doubled to the tetraploid value by the onset of mitosis, although the chromosome number is still diploid. During mitosis, this amount is halved between the two daughter cells, so that DNA quantity and chromosome number are diploid in both cells. The nuclear changes that achieve this distribution are conventionally divided into four phases called prophase, metaphase, anaphase and telophase  PROPHASE During prophase, the strands of chromatin, which are highly extended during interphase, shorten, thicken and resolve themselves into recognizable chromosomes. Each chromosome is made up of duplicate chromatids joined at their centromeres. Outside the nucleus, the two centriole pairs begin to separate, and move towards opposite poles of the cell.  PROPHASE Parallel microtubules are assembled between them to create the mitotic spindle, and others radiate to form the asters, which come to lie at the spindle poles. As prophase proceeds, the nucleoli disappear, and the nuclear membrane suddenly disintegrates into small vesicles to release the chromosomes, an event that marks the end of prophase  PROMETAPHASE-METAPHASE As the nuclear membrane disappears, the spindle microtubules extend into the central region of the cell, attaching to the chromosomes which move towards the equator of the spindle (prometaphase). This plane is called the metaphase or equatorial plate. The chromosomes, attached at their centromeres, appear to be arranged in a ring when viewed from either pole of the cell, or to lie linearly across this plane when viewed from above. metaphase  ANAPHASE The centromere in metaphase is a double structure (one per sister chromatid). During anaphase its halves separate, each carrying an attached chromatid. Each original chromosome appears therefore to split lengthwise into two new chromosomes, which move apart, one towards each pole. At the end of anaphase the chromosomes are grouped at either end of the cell, and both clusters are diploid in number. An infolding of the cell equator begins, and deepens during telophase as the cleavage furrow ANAPHASE  During telophase the chromosomes decondense. Each nuclear membrane forms, beginning as membranous vesicles at the ends of the chromosomes, and the nucleoli appear.  TELOPHASE At the same time, cytoplasmic division, which usually begins in early anaphase, continues until the new cells separate, each with its derived nucleus The spindle remnant now disintegrates. While the cleavage furrow is active, a peripheral band or belt of actin and myosin appears in the constricting zone: contraction of this band is responsible for furrow formation.  Failure of disjunction of chromatids, so that paired chromatids pass to the same pole, may sometimes occur. Of the two new cells, one will have more, and the other fewer, chromosomes than the diploid number. Exposure to ionizing radiation promotes non- disjunction and may, by chromosomal damage, inhibit mitosis altogether These compounds inhibit or reverse spindle microtubule formation, so that mitosis is arrested in metaphase. This underpins the rationale for many types of cytotoxic drugs used in cancer therapy. summary  MEIOSIS There are two cell divisions during meiosis. Details of this process differ at a cellular level for male and female lineages Meiosis involves one reduplication of the chromosomes followed by two sequential cell divisions. Thus a diploid cell produces four haploid germ cells (gametes). Crossing over occurs only in meiosis, to rearrange alleles such that every gamete is genetically different. In contrast,the products of mitosis are genetically identical  The process of sexual reproduction involves the production by meiosis of specialised male and female cells called gametes; Meiotic cell division is thus also called gametogenesis. Each gamete contains the haploid number of chromosomes (23 in humans), i.e. one from each homologous pair.  The process of meiosis involves many of the mechanisms and control systems that regulate mitosis. The process of meiosis is outlined below and compared to mitosis Before meiosis can begin, the chromosomes are duplicated as for mitosis (meiotic S phase). This is immediately followed by crossing over of the chromatids, so that genetic information is exchanged between the two chromosomes of the homologous pair.  As one of each pair of chromosomes is derived from the father and one from the mother, crossing over mixes up these paternally and maternally derived alleles (alternative forms of the same gene) so that the haploid gamete ends up with only one of each chromosome pair, but each individual chromosome includes alleles from each parent  The mechanism of crossing over is called chiasma formation. This phase is known as prophase I. As well as generating great genetic diversity, this mixing up of genes explains the conviction of many teenagers that they must be adopted.  Prophase I Leptotene stage Chromosomes appear as Prophase I is a long and individual threads that complex phase that differs are attached at one end considerably from mitotic to the nuclear membrane. prophase and is customarily divided into five substages, They show characteristic called leptotene, zygotene, beading throughout their pachytene, diplotene and length. diakinesis. Their DNA has been replicated in the preceding S phase  Zygotene stage Chromosomes lie together side by side in homologous pairs, a process which may be initiated during the previous mitotic division. The homologous chromosomes pair point for point progressively, beginning at their attachment to the nuclear membrane, so that corresponding regions lie in contact. This process is known as synapsis, conjugation or pairing, and each pair is now a bivalent. In the case of the unequal X and Y sex chromosomes, only limited pairing segments are homologous and these pair end to end. Homologous chromosomes are held together by a highly structured fibrillar band, the synaptonemal complex.  Pachytene stage As shortening and thickening of each chromosome progress, its two chromatids, which are joined at the centromere, become visible. Each bivalent pair therefore consists of four chromatids, forming a tetrad. Two chromatids, one from each bivalent chromosome, partially coil round each other, and during this stage, exchange of DNA (crossing over or decussating) occurs by breaking and rejoining of strands  Diplotene stage Homologous pairs, now much shortened, separate except where crossing over has occurred (chiasmata). At least one chiasma forms between each homologous pair and up to five have been observed. In the ovaries, primary oocytes become diplotene by the fifth month in utero and each remains at this stage until the period before ovulation (up to 50 years).  Diakinesis The chromosomes, still as bivalents, become even shorter and thicker. They subsequently disperse, as bivalents, to lie against the nuclear membrane. During prophase, the nucleoli disappear and the spindle and asters form as they do in mitosis. At the end of prophase the nuclear membrane disappears and bivalent chromosomes move towards the equatorial plate (prometaphase).  Metaphase I Metaphase I resembles mitotic metaphase, except that the bodies attaching to the spindle microtubules are bivalents, not single chromosomes. These become arranged so that the homologous pairs lie parallel to the equatorial plate, with one on either side. Anaphase and telophase I Chiasmata finally disappear. Anaphase and telophase I also occur as in mitosis, except that in anaphase the centromeres do not split. Instead of paired chromatids separating to move towards the poles, entire homologous chromosomes move to opposite poles. As positioning of bivalent pairs is random, assortment of maternal and paternal chromosomes in each telophase nucleus is also random.  MEIOSIS II Meiosis II commences after only a short interval during which no DNA synthesis occurs. This second division is more like mitosis, in that chromatids separate during anaphase, but, unlike mitosis, the separating chromatids are genetically different. Cytoplasmic division also occurs and thus, in the male, four haploid cells result from meiosis I and II.  Apoptosis Apoptosis is a rapid, highly regulated cellular activity that shrinks and eliminates defective and unneeded cells It results in small membrane enclosed apoptotic bodies, which quickly undergo phagocytosis by neighboring cells or cells specialized for debris removal. Apoptotic cells do not rupture and release none of their contents, unlike damaged cells that undergo necrosis as a result of injury.  This difference is highly significant because release of cellular components triggers a local inflammatory reaction andimmigration of leukocytes. Such a response is avoided when cells are routinely and rapidly eliminated following DNA damage or as part of normal organ development by apoptosis. Apoptosis is controlled by cytoplasmic proteins in the Bcl-2 family, which regulate the release of death-promoting factors from mitochondria.  Activated by either external signal or irreversible internal damage, specific Bcl-2 proteins induce a process with the following features: Loss of mitochondrial function and caspase activation Bcl-2 proteins associated with the outer mitochondrial membrane compromise membrane integrity, stopping normal activity and releasing cytochrome c into the cytoplasm where it activates proteolytic enzymes called caspases. The initial caspases activate a cascade of other caspases, resulting in protein degradation throughout the cell  Fragmentation of DNA Endonucleases are activated,which cleave DNA between nucleosomes into small fragments. (The new ends produced in the fragmented DNA allow specific histochemical staining of apoptotic cells using an appropriate enzyme that adds labeled nucleotides at these sites.)  Shrinkage of nuclear and cell volumes: Destruction of the cytoskeleton and chromatin causes the cell to shrink quickly, producing small structures with dense, darkly stained pyknotic nuclei that may be identifiable with the light microscope Cell membrane changes: The plasma membrane of the shrinking cell undergoes dramatic shape changes, such as “blebbing,” as membrane proteins are degraded and lipid mobility increases. Formation and phagocytic removal: Membrane-bound remnants of cytoplasm and nucleus separate as very small apoptotic bodies Newly exposed phospholipids on these bodies induce their phagocytosis by neighboring cells or white blood cells.  MEDICAL APPLICATION Retinoblastoma is a type of cancer occurring in the eyes, usually in young children Cancer cells often deactivate the genes that control the apoptotic process, thus preventing their elimination in this type of cell death and allowing progression toward a more malignant state  Failure of clonal deletion may lead to autoimmune disorders such as autoimmune thyroiditis or pernicious anaemia. Examination of the chromosomes of dividing cells, karyotyping, can give diagnostic information about the chromosomal complement of an individual or of a malignant tumour  THE END THANK YOU FOR LISTENING