The Cell Cycle (Mitosis) PDF

The Cell Cycle Soner Dogan, PhD Professor of Medical Biology Biology Eighth Edition Yeditepe University Neil Campbell and Jane Reece School of Medicine PowerPoint® Lecture Presentations for • Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pea...

The Cell Cycle Soner Dogan, PhD Professor of Medical Biology Biology Eighth Edition Yeditepe University Neil Campbell and Jane Reece School of Medicine PowerPoint® Lecture Presentations for • Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings What to know for this lecture • How do a cell’s chromosomes change during cell division? • Differences between mitosis and meiosis • Check points • MPF • You should be able to draw cell cycle with each phases • Terminology: Aster, centromere, centrosome, kinetochores, Cohesins, spindle fiber, microtubule, How do a cell’s chromosomes change during cell division? • 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 (a) Reproduction (b) Growth and development (c) Tissue renewal Cellular Organization of the Genetic Material • 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 20 µm • 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 • Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division Chromosomes = condensed chromatin (DNA + proteins) Distribution of Chromosomes During Eukaryotic Cell Division • In preparation for cell division, DNA is replicated and the chromosomes condense • Each duplicated chromosome has two sister chromatids, which separate during cell division • The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached 0.5 µm Chromosomes Chromosome arm DNA molecules Chromosome duplication (including DNA synthesis) Centromere Sister chromatids Separation of sister chromatids Centromere Sister chromatids •Each duplicated chromosome has two sister chromatids, which separate during cell division Phases of the Cell Cycle G1 S (DNA synthesis) G2 • Eukaryotic cell division consists of: – Interphase (cell growth and copying of chromosomes in preparation for cell division) – Mitosis, the division of the nucleus – Cytokinesis, the division of the cytoplasm • Mitotic (M) phase (mitosis and cytokinesis) • Gametes are produced by a variation of cell division called meiosis • Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell Phases of the Cell Cycle • Interphase (about 90% of the cell cycle) can be divided into subphases: – G1 phase – S phase – G2 phase • The cell grows during all three phases, but chromosomes are duplicated only during the S phase Phases of Mitosis • Mitosis is conventionally divided into five phases: – Prophase – Metaphase – Anaphase – Telophase • Cytokinesis is well underway by late telophase Mitosis Chapter 11 in Biol Cell Cycle • G1 phase, – accumulates materials needed to replicate DNA • S phase, synthesis phase – DNA replication ****** • G2 phase, – replicates centrioles – synthesizes enzymes for division • M phase, mitotic phase – nuclear and cytoplasmic division • G0 phase, cells that have left the cycle • Cell cycle duration varies between cell types Mitosis • one cell divides into 2 daughter cells with identical copies of DNA • Functions of mitosis – embryonic development – tissue growth CELL PROLIFERATION – replacement of dead cells – repair of injured tissues • Phases of mitosis (nuclear division) – prophase, metaphase, anaphase, telophase Cell at Interphase •Telophase •Anaphase •nucleus •cytoplasm •Prophase •Metaphase The Four Stages of Mitosis • Mitosis begins with prophase. – Chromosomes start condensing to become visible as rod like units, each consisting of two sister chromatids joined at the centromere.  The spindle starts forming from reassembled microtubules of the cytoskeleton.  The spindle separates the centrioles to opposite poles of the cell. Mitosis: Prophase cont. • Nuclear envelope disintegrates • Centrioles sprout microtubules that push them apart and towards each pole of the cell – spindle fibers grow towards chromosomes • attach to kinetochore on side of centromere – spindle fibers pull chromosomes towards cell equator Mitosis: Metaphase • Chromosomes line up on one equator • Mitosis spindles finished – spindle fibers (microtubules) attach centrioles to long centromere – shorter microtubules anchor centrioles to plasma membrane (aster) •4-18 TERMINOLOJI • Sister chromatids are held together by protein complexes called Cohesins. • Defects in sister chromatid cohesin leads to major errors in chromosome segregation. • The centrosome is the principle microtubuleorganizing center in animal cells. It dublicates. • Aster- group of microtubules • Kinetochores- protein complexes that assemble on the centromere of each condensed chromosome during late prophase. Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm Mitosis: Anaphase • Enzyme splits 2 chromatids apart at centromere • Daughter chromosomes move towards opposite poles of cells with centromere leading the way – motor proteins in kinetochore move centromeres along spindle fibers as fibers are disassembled Mitosis: Telophase • New nuclear envelopes formed by rough ER • Chromatids uncoil into chromatin (they “decondense”). • Mitotic spindle breaks down • Nucleus forms nucleoli • In mitosis, each new cell has the same chromosome number as the parent nucleus. Cell at Interphase •Telophase •Anaphase •nucleus •cytoplasm •Prophase •Metaphase Cytokinesis • Division of cytoplasm into 2 cells – overlaps telophase • Myosin pulls on microfilaments of actin in the membrane skeleton – creates crease around cell equator called cleavage furrow • Cell pinches in two – interphase has begun • Each new cell has a nucleus, cytoplasm, and a plasma membrane. Cleavage furrow •4- Cytokinesis in animal and plant cells 100 µm Cleavage furrow Contractile ring of microfilaments (a) Cleavage of an animal cell (SEM) Vesicles forming cell plate Wall of parent cell Cell plate 1 µm New cell wall Daughter cells Daughter cells (b) Cell plate formation in a plant cell (TEM) Timing of Cell Division Cells divide when: • Have enough cytoplasm for 2 daughter cells • DNA replicated • Adequate supply of nutrients • Growth factor stimulation • Open space due to neighboring cell death Cells stop dividing when: • Loss of growth factors or nutrients • Contact inhibition •4- Density-dependent inhibition and anchorage dependence of cell division ---------------------------------------------------------------------------------------------Anchorage dependence Density-dependent inhibition Density-dependent inhibition 25 µm 25 µm (a) Normal mammalian cells (b) Cancer cells • Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence !!!!!!!!!!! G2 of Interphase Chromatin Centrosomes (with centriole (duplicated) pairs) Prophase Early mitotic Aster Centromere spindle Nucleolus Nuclear Plasma envelope membrane Chromosome, consisting of two sister chromatids Prometaphase Fragments Nonkinetochore of nuclear microtubules envelope Kinetochore Kinetochore microtubule Metaphase Anaphase Telophase and Cytokinesis Metaphase Anaphase Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm The eukaryotic cell cycle is regulated by a molecular control system • The frequency of cell division varies with the type of cell • These cell cycle differences result from regulation at the molecular level Evidence for Cytoplasmic Signals • The cell cycle appears to be driven by specific chemical signals present in the cytoplasm • Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei The Cell Cycle Control System • The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock • The cell cycle control system is regulated by both internal and external controls • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received G1 checkpoint Control system G1 M S G2 S checkpoin M checkpoint G checkpoint • For many cells, the G1 checkpoint seems to be the most important one • If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G 2, and M phases and divide • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase •The G1 checkpoint G0 G1 checkpoint G1 (a) Cell receives a go-ahead signal G1 (b) Cell does not receive a go-ahead signal https://www.healthgrades.com/right-care/cancer/howcheckpoint-inhibitors-fight-cancer?p=1&cid=t1_rss12_2 The Cell Cycle Clock:Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) • The activity of cyclins and Cdks fluctuates during the cell cycle • MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G 2 checkpoint into the M phase Regulators of Cell Cycle Progression • When MPF was purified and shown to composed of two subunits: Cdk1 and cyclin B. • Cyclin B is a regulatory subunit required for catalytic activity of the Cdk1 protein kinase. Regulators of Cell Cycle Progression • Further studies demonstrated the regulation of MPF by phosphorylation and dephosphorylation of Cdk1. • Cyclin B is synthesized and forms complexes with Cdk1 during G2. • Cdk1 is phosphorylated and inhibited, leading to accumulation of inactive Cdk1/cyclin B complexes throughout G2. Regulators of Cell Cycle Progression • Dephosphorylation activates Cdk1, which phosphorylates several proteins that initiate the events of M phase. • Cyclin B is degraded by ubiquitin-mediated proteolysis. MPF regulation Stop and Go Signs: Internal and External Signals at the Checkpoints • An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase • Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture Density-dependent inhibition and anchorage dependence of cell division ---------------------------------------------------------------------------------------------Anchorage dependence Density-dependent inhibition Density-dependent inhibition 25 µm 25 µm (a) Normal mammalian cells (b) Cancer cells • Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence !!!!!!!!!!! Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond normally to the body’s control mechanisms • Cancer cells may not need growth factors to grow and divide: – They may make their own growth factor – They may convey a growth factor’s signal without the presence of the growth factor – They may have an abnormal cell cycle control system The growth and metastasis of a malignant breast tumor Lymph vessel Tumor Blood vessel Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring tissue. Cancer cell Metastatic tumor 4 Cancer cells may 3 Cancer cells spread to other parts of survive and the body. establish a new tumor in another part of the body.