Cell Cycle and Mitosis 2024-2025 PDF

Cell Cycle and Mitosis Asst. Prof. Burcu TÜRKGENÇ Dept. of Medical Biology  The beginning……. Ovum Zygote Its nucleus The nucleus from the contains 23 sperm fuses with the chrom...

Cell Cycle and Mitosis Asst. Prof. Burcu TÜRKGENÇ Dept. of Medical Biology  The beginning……. Ovum Zygote Its nucleus The nucleus from the contains 23 sperm fuses with the chromosomes ovum nucleus – now + there are 46 chromosomes in the cell (23 pairs) Sperm Its nucleus contains 23 Millions of cells will chromosomes be produced from this beginning 2  Introduction In unicellular organisms, division of one cell reproduces the entire organism. Multicellular organisms depend on cell division for – Development from a fertilized cell – Growth – Repair Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division. 3  Introduction All the DNA in a cell constitutes the cell’s genome. A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells) DNA molecules in a cell are packaged into chromosomes. 4 5  Introduction Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division. Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus. Somatic cells (nonreproductive cells) have two sets of chromosomes. Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells.6 7  Introduction In preparation for cell division, DNA is replicated and the chromosomes condense. Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), which separate during cell division. The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached. 8  Chromosomal Chromosomes DNA molecules 1 Centromere Introduction Chromosome During cell division, the arm two sister chromatids Chromosome duplication (including DNA replication) of each duplicated and condensation 2 chromosome separate and move into two nuclei. Sister chromatids Once separate, the Separation of sister chromatids into chromatids are called two chromosomes 3 chromosomes. 9  Introduction The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis. In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center. The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase. 10  Introduction An aster (a radial array of short microtubules) is a cellular structure shaped like a star, extends from each centrosome. The spindle includes the centrosomes, the spindle microtubules, and the asters. During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes. Kinetochores are protein complexes associated with centromeres. At metaphase, the chromosomes are all lined up at the metaphase plate, an imaginary structure at the midway point between the spindle’s two poles. 11  Centrosome Aster Metaphase Sister plate chromatids (imaginary) Microtubules Chromosomes Kineto- chores Centrosome 1 m Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 m 12  Introduction Eukaryotic cell division consists of – Mitosis, the division of the genetic material in the nucleus. – Cytokinesis, the division of the cytoplasm. Gametes are produced by a variation of other cell division called meiosis. Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell. 13 Link the terms with the correct definition 1 Organelle in animal cells which produces the spindle A centrosome (nonreproductive cells) have two 2 B nucleolus sets of chromosomes. 3 Cell(s) produced as a result of C Sister fertilization chromatids 4 Ribosome production factory D histone Pairs of identical copies formed by 5 E zygote the DNA replication of a chromosome F karyotype 6 Picture of the chromosomes from a cell G somatic cells Any of the numbered or nonsex 7 chromosomes of an organism H autosomes 8 Protein around which DNA strands coil 14 Link the terms with the correct definition 1 Organelle in animal cells which produces the spindle A centrosome (nonreproductive cells) have two 2 B nucleolus sets of chromosomes. 3 Cell(s) produced as a result of C Sister fertilization chromatids 4 Ribosome production factory D histone Pairs of identical copies formed by 5 E zygote the DNA replication of a chromosome F karyotype 6 Picture of the chromosomes from a cell G somatic cells Any of the numbered or nonsex 7 chromosomes of an organism H autosomes 8 Protein around which DNA strands coil 15  Cell Division There are two kinds of cell division 1-Mitosis ;Division of somatic cells 2-Meiosis; Production of germ cells 16  Mitosis In 1879, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis (by light microscope) and used the term mitosis Mito ; means thread to describe long thread like chromosomes. 17  Mitotic Cell Division is required; 1-During development to make a new individual. As a result of the successive divisions of fertilized egg; Zygot 3.7 × 1013 (37 trillion) cells are produced that make up the human body. 2-For normal growth 3-In the adult body; for renewal, regeneration, repair to replace cells that are lost by wear and tear and by programmed cell death (for the maintenance of individual) 18  Frequency of Cell Division by Mitosis How often the cell divides Varies with the cell type; 1- Some cells divide frequently throughout life; Rapidly renewing cells; (once a day) Epithelium of the skin Intestinal epithelial cells 19  Frequency of Cell Division by Mitosis 2-Some other cells divide very rarely Liver cells, Pancreas After an injury liver cells rapidly divide to repair a wound (until normal volume of the liver is restored) 3-Some cells never divide (long lived) in a mature human. Nerve cells Hearth muscle cells 20  Mitosis Aim; to produce two genetically identical daughter cell. Somatic cells are diploid (2n). As a result of the division of a diploid parent cell two diploid (2n) daughter cells are produced. 21  In each division-cycle To produce two genetically identical daughter cells. A cell must replicate (duplicate) its DNA. Most cells must grow and duplicate all of their cytoplasmic contents. They must segregate duplicated chromosomes to daughter cells. 22  Cell Cycle The cell cycle – Cellular events in sequence from one division to another – Phases of cell cycle Interphase G1 S phase G2 M phase 23  Phases of the Cell Cycle The cell cycle consists of – Mitotic (M) phase (mitosis and cytokinesis) – Interphase (cell growth and copying of chromosomes in preparation for cell division) Interphase (about 90% of the cell cycle) can be divided into subphases: – G1 phase (“first gap”) – S phase (“synthesis”) – G2 phase (“second gap”) The cell grows during all three phases, but chromosomes are duplicated only during the S phase. 24  INTERPHASE G1 S (DNA synthesis) G2 25  Interphase G1 (First Gap Period) – Cell grows and increases in mass. Cell membrane is increased. Number of organelles increases. Chemical preparation for DNA Synthesis. (enzymes, deoxyribose sugars, nucleotide bases and phosphates synthesised) Its length can vary greatly depending on external conditions and extracellular signals from other cells. *RNA synthesis (transcription) and protein synthesis 26 (translation) occurs.  Interphase G1 (First Gap Period) If extracellular conditions are unfavorable, cells do not progress through G1 and may enter a resting state known as G0 (G zero) Cells that stop proliferating enter G0. Cancer cells are unable to enter G0 and cycle continuously. *Differentiated cells (e.g., nerve cells and heart muscle cells) can not exit the G0 and perform their main functions indefinitely. 27  Interphase S phase (synthesis) – Replication of DNA. Chromosomes held together by centromere – In animals centriole pairs duplicate. – At the end of S phase DNA amount is doubled ; 4n (tetraploid). 28  Interphase G2 (Second gap phase) – Cell builds up energy reserves – RNA synthesis (transcription) and protein synthesis (translation) occurs. – Cell growth continues. – Proteins are synthesized in preparation for mitosis (i.e Tubulin). – Cell contains 4n DNA (post duplication Phase). 29  Cell Cycle Control and Checkpoints G1/S, G2/M, and M checkpoints – Three distinct checkpoints where the cell monitors external signals and internal equilibrium. – Cells decide whether to proceed to the next stage of the cell cycle. – and loss of cell cycle checkpoint control promotes genetic instability. 30 These checkpoints are regulated by proteins such as cyclins and cyclin-dependent kinases (Cdks). Cyclins proteins drive the events of the cell cycle by partnering with a family of enzymes called the cyclin-dependent kinases (Cdks). Alone Cdk is inactive, but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins. 31 Cyclin-CDK complexes being formed and activated at different phases of the cell cycle to regulate cell cycle. These complexes are essential for maintaining the accuracy of cell division and preventing genomic instability. Cyclin-Cdk activity is also regulated by Cdk inhibitors (CKIs), which are proteins that bind to cyclin-Cdk complexes and inhibit their activity. For example: p21 is a well-known CKI that inhibits Cyclin D-Cdk4/6 and Cyclin E-Cdk2 complexes. At the G1 checkpoint, the cell checks if the conditions are right for DNA replication. If DNA damage is detected, At the G2 checkpoint, the cell checks if p53 activates the expression DNA replication has been completed of p21, which inhibits Cyclin- correctly. If damage is detected, the Cyclin CDK complexes, halting B-Cdk1 complex is inhibited to delay progression into S phase. mitosis until repair is complete. 32  Mitosis Division of somatic cells Mitosis is a process where a single cell divides into two identical daughter cells Key event of mitosis 1 - Chromosome condensation 2 - Formation of mitotic spindle 3 - Sister chromatid separation 33  Chromosome condensation Condensation of interphase chromatin to form the compact chromosomes is a key event of mitosis. Required to enable the chromosomes to move along the mitotic spindle without becoming broken or tangled with one another. Chromatin condenses a thousand fold during formation of metaphase chromosomes. 34 Mitosis; Morphological stage (M phase)  RNA and protein synthesis DO NOT occur The Events of M phase. Cell structure undergoes dramatic alterations; 1-Chromosomes condense 2-Nuclear envelope breaks down 3-The cytoskeleton reorganizes to form mitotic spindle. 4-Duplicated chromosomes (sister chromatids) separate and move to opposite poles. 5-Two daughter nuclei form 6-Cytoplasm divides (Cytokinesis). 35  Mitosis (nuclear division) Mitosis consists of 6 stages 1) Prophase 2) Prometaphase 3)Metaphase 4)Anaphase 5)Telophase 6)Cytokinesis 36 37 38  1 - Prophase Nucleus Beginning of prophase is marked by ; 1 - Appearance of condensed chromosomes (Long, thin thread like structures) Each chromosome consists of two sister chromatids (produced in S phase), Chromatids attach together firmly by cohesins that links the chromatids). 2 - Nucleolus disappears. 3 - Breakdown of nuclear envelope marks the end of Prophase. Joins onto spindle fibre Chromatids in condensed form 39 40  1 - Prophase Cytoplasm Development of mitotic spindle initiates. Cytoskeleton disintegrates (its components (microtubules) are used to begin spindle formation) Centrosomes (which were duplicated during S phase) separate and move to opposite sites of the nucleus. They will serve as opposite poles of the mitotic spindle. 41  2 - Prometaphase A transition period between prophase and metaphase. Further condensation of the chromosomes occurs. Chromosomes can be seen as thicker and shorter structures. 42  2 - Prometaphase The microtubules of the mitotic spindle attach to the kinetochores of chromosomes (Kinetochores of sister chromatids attach to microtubules emanating from opposite poles of spindle.) Chromosomes move back and forward until they align on the metaphase plate. 10 m G2 of Interphase Prophase Prometaphase 43  G2 of Interphase Prophase Prometaphase Centrosomes Fragments (with centriole Chromatin Early mitotic Aster of nuclear Nonkinetochore pairs) (duplicated) spindle envelope microtubules Centromere Plasma Nucleolus membrane Kinetochore Kinetochore Chromosome, consisting Nuclear of two sister chromatids microtubule envelope 44  3 - Metaphase Chromosomes align on the metaphase plate in the center of the spindle. Cells remain only briefly at metaphase. Two sister chromatids are held together only at the centromere 45  3 - Metaphase Spindle continues to grow from centrosomes (which are now at the poles) Chromosomes attach to the spindle fibers by the kinetochore in the centromere. The arrangement of the chromosomes across the equator is also known as the metaphase plate. 46  Metaphase Chromosome Metaphase: Chromatin becomes even more condensed and sister chromatids line up along the mid-region of the cell or the metaphase plate. To obtain metaphase chromosomes from cells (for example: white blood cells from blood), the cells are isolated, cultured, and treated with colchicine to arrest cell division at metaphase. The cells are then fixed, and the chromosomes are spread on slides for observation under a microscope. This process is essential for techniques such as karyotyping to study chromosomal abnormalities. 47  Metaphase Chromosome (a) A metaphase spread image and (b) the corresponding karyotype image that homologous chromosomes arranged side by side. 48  Metaphase Chromosome Homologous chromosomes are pairs of chromosomes in a diploid organism come from different parent. These sister chromatids are formed during the S phase of the cell cycle, through the process of DNA replication. This process ensures that each daughter cell receives an exact copy of the genetic information during mitosis. *Sister chromatids are identical copies of each chromosome, connected by the centromere. 49  Anaphase Transition from metaphase to anaphase triggered by breakdown of the links between sister chromatids (degradation of cohesins that links the chromatids) Then sister chromatids separate and move to opposite poles of the spindle 50  Anaphase Centromeres divide. The microtubules shorten by depolymerizing at their kinetochore ends. 51  Telophase Chromosomes decondense. Division of nucleus ends with telophase. Nuclei reform (nuclear envelope reform) Cytokinesis begins during anaphase. Cytokinesis is complete by the end of telophase. 52 53  Metaphase Anaphase Telophase and Cytokinesis Metaphase Cleavage Nucleolus plate furrow forming Nuclear Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming 54 55  Cytokinesis Completion of mitosis give rise to two daughter cells. Cytokinesis begins during anaphase. Mediated by a contactile ring of actin and myosin II filaments that forms beneath the plasma membrane at the equatorial plate of the spindle. *Division of cytoplasm 56  Cytokinesis Cleavage proceeds as contraction of actin-myosin filaments pulls the membrane inward and divide the cell in half. 57 58 59 60