BIOL 110 Chapter 12 Cell Cycle PDF

BIOL 110 Chapter 12 Cell Cycle  Key Roles of Cell Division The ability of organisms to produce more of their own kind best distinguishes living things from nonliving matter The continuity of life is based on the reproduction of cells, or cell division  Unicellular organism...

BIOL 110 Chapter 12 Cell Cycle  Key Roles of Cell Division The ability of organisms to produce more of their own kind best distinguishes living things from nonliving matter The continuity of life is based on the reproduction of cells, or cell division  Unicellular organisms, 100 µm (a) Reproduction division of 1 cell reproduces entire organism Multicellular organisms depend on 200 µm cell division for (b) Growth and development – Development from fertilized cell – Growth – Repair Cell division is integral part of cell cycle, the life of a cell from formation 20 µm to its own division (c) Tissue renewal  Cell Division/Genetic Material Most cell division results in daughter cells with identical genetic information (DNA) The exception is meiosis, a special type of division that can produce sperm and egg cells – why is this an exception? All the DNA in a cell constitutes the cell’s genome A genome can consist of a single DNA molecule (prokaryotic cells) or a number of DNA molecules (eukaryotic cells) DNA molecules in a cell packaged into chromosomes  Eukaryotic Chromosomes Eukaryotic chromosomes consist of chromatin, a complex of DNA & protein 20 µm that condenses during cell division Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus Somatic cells (nonreproductive cells) have 2 sets of chromosomes Gametes (reproductive cells: sperm & eggs) have half as many chromosomes as somatic cells  Eukaryotic Chromosomes/Cell Division In preparation for cell division, DNA is replicated & chromosomes condense Each duplicated chromosome has 2 sister chromatids (joined copies of the original chromosome), which separate during cell division Centromere - narrow “waist” of duplicated chromosome, where the 2 chromatids are most closely attached Sister chromatids Centromere 0.5 µm  Chromosomes Chromosomal DNA molecules During cell division, 1 Centromere the 2 sister chromatids of each duplicated Chromosome arm chromosome separate & move into 2 nuclei Chromosome duplication (including DNA replication) and condensation 2 Once separate, chromatids are called chromosomes Sister chromatids Separation of sister Each new nucleus chromatids into two chromosomes receives a group of 3 chromosomes identical to the original group in the parent cell.  Eukaryotic Chromosomes/Cell Division Eukaryotic cell division consists of – Mitosis, division of the genetic material in nucleus – Cytokinesis, division of the cytoplasm Fertilized egg - cycles of mitosis and cytokinesis to produce a fully developed multicellular human made up of 200 trillion somatic cells Gametes are produced by a variation of cell division called meiosis Meiosis yields nonidentical daughter cells that have only 1 set of chromosomes, half as many as the parent cell – how do we get back to 2 sets of chromosomes?  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  Cell Cycle INTERPHASE G1 S (DNA synthesis) G2 Cell Cycle P G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase  Mitosis Mitosis is conventionally divided into five phases – Prophase – Prometaphase – Metaphase – Anaphase – Telophase Cytokinesis overlaps the latter stages of mitosis 10 µm G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase and Cytokinesis Centrosomes Chromatin Fragments Nonkinetochore (with centriole pairs) (duplicated) Early mitotic Aster of nuclear microtubules Metaphase Cleavage Nucleolus spindle Centromere envelope plate furrow forming Plasma Nucleolus Nuclear membrane Chromosome, consisting Kinetochore Kinetochore Nuclear envelope of two sister chromatids microtubule Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming  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 10 µm G2 of Interphase Prophase Prometaphase  Metaphase Anaphase Telophase and Cytokinesis Metaphase Cleavage Nucleolus plate furrow forming Nuclear Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming 10 µm Metaphase Anaphase Telophase and Cytokinesis  Mitotic Spindle Mitotic spindle - structure made of microtubules, controls chromosome movement during mitosis – Animal cells, assembly of spindle microtubules begins in centrosome - microtubule organizing center The centrosome replicates during interphase, forming 2 centrosomes that migrate to opposite ends of the cell during prophase & prometaphase An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, & the asters  Mitotic Spindle During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes & begin to move the chromosomes Kinetochores - 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 2 poles  Mitotic Spindle Centrosome Aster Metaphase Sister plate chromatids (imaginary) Microtubules Chromosomes Kineto- chores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm  Mitotic Spindle EXPERIMENT Kinetochore In anaphase, sister chromatids Spindle pole separate & move along the kinetochore microtubules toward opposite ends of the cell Mark The microtubules shorten by depolymerizing at their kinetochore ends RESULTS Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell CONCLUSION Chromosome movement In telophase, genetically identical Microtubule Kinetochore daughter nuclei form at opposite Motor protein Tubulin ends of the cell Chromosome subunits  Cytokinesis Cytokinesis begins during anaphase or telophase & the spindle eventually disassembles Animal cells: cytokinesis occurs by cleavage, forming a cleavage furrow Plant cells, a cell plate forms during cytokinesis (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM) 100 µm Cleavage furrow Vesicles forming Wall of parent cell 1 µm cell plate Cell plate New cell wall Contractile ring of Daughter cells microfilaments Daughter cells  Mitosis in a Plant Cell Chromatin Nucleus condensing 10 µm Nucleolus Chromosomes Cell plate 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase Mitosis in a Plant Cell  Binary Fission in Bacteria Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart The plasma membrane pinches inward, dividing the cell into two Binary Fission Origin of replication Cell wall Plasma membrane E. coli cell Bacterial chromosome 1 Chromosome Two copies replication of origin begins. 2 Replication Origin Origin continues. 3 Replication finishes. 4 Two daughter cells result.  Regulation of Eukaryotic Cell Cycle The frequency of cell division varies with the type of cell – Some human cells divide frequently throughout life (skin cells) – Others human cells have the ability to divide but keep it in reserve (liver cells) – Mature nerve and muscle cells do not appear to divide at all after maturity These differences result from regulation at the molecular level Cancer cells manage to escape the usual controls on the cell cycle 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 EXPERIMENT Experiment 1 Experiment 2 S G1 M G1 RESULTS What do these results tell us? S S M M When a cell in the S When a cell in the phase was fused M phase was fused with with a cell in G1, a cell in G1, the G1 the G1 nucleus nucleus immediately immediately entered began mitosis—a spindle the S phase—DNA formed and chromatin was synthesized. condensed, even though the chromosome had not been duplicated.  Cell Cycle Control System The sequential events of cell cycle are directed by a distinct cell cycle control system (clock) – regulated by both internal and external controls – has specific checkpoints where the cell cycle stops until a go-ahead signal is received Animal cells generally have built-in stop signals that halt the cell cycle at checkpoints until they are overridden by go-ahead signals. Many signals registered at checkpoints come from cellular surveillance mechanisms – These mechanisms indicate whether key cellular processes have been completed correctly – Checkpoints also register signals from outside the cell – three major checkpoints are found in the G1, G2, and M phases  Cell Cycle Control System G1 checkpoint Control system S G1 M G2 M checkpoint G2 checkpoint  Cell Cycle Control System For many cells, G1 checkpoint seems most important If cell receives go-ahead signal at G1 checkpoint, it will usually complete the S, G2, and M phases & divide If cell does not receive go-ahead signal, it will exit cycle, switching into a non- dividing state = G0 phase G0 G1 checkpoint G1 G1 (a) Cell receives a go-ahead (b) Cell does not receive a signal. go-ahead signal. The Cell Cycle Clock: M G1 S G2 M G1 S G2 M G1 Cyclins & Cyclin- MPF activity Cyclin Dependent Kinases concentration 2 types of regulatory proteins Time are involved in cell cycle control: (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle cyclins & cyclin-dependent kinases (Cdks) Cdks activity fluctuates during cell cycle because it is controlled by cyclins Cdk Degraded MPF (maturation-promoting cyclin G2 checkpoint Cdk factor) = cyclin-Cdk complex Cyclin is degraded that triggers a cell’s passage MPF Cyclin past G2 checkpoint into M phase (b) Molecular mechanisms that help regulate the cell cycle Internal and external cues Example of internal signal - kinetochores not attached to help regulate the cell spindle microtubules send a molecular signal that delays cycle anaphase 1 A sample of human Scalpels connective tissue is External signals - growth cut up into small factors, proteins released by pieces. certain cells that stimulate Petri other cells to divide dish 2 Enzymes digest – Example: platelet-derived growth the extracellular factor (PDGF) stimulates division matrix, resulting in of human fibroblast cells in a suspension of culture free fibroblasts. 4 PDGF is added 10 µm 3 Cells are transferred to to half the culture vessels. vessels. Without PDGF With PDGF  External cues help regulate the cell cycle External signal: density-dependent inhibition, in which crowded cells stop dividing Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence – so what does this mean?  External cues help regulate the cell cycle Anchorage dependence Density-dependent inhibition Density-dependent inhibition 20 µm 20 µm (a) Normal mammalian cells (b) Cancer cells  Loss of Cell Cycle Controls in Cancer Cells Cancer cells – do not respond normally to the body’s control mechanisms – may not need growth factors to grow & 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 Normal cell converted to cancerous cell by transformation Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue If abnormal cells remain only at original site, lump is benign tumor Malignant tumors invade surrounding tissues & can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors Loss of Cell Cycle Controls in Cancer Cells Lymph vessel Tumor Blood vessel Glandular Cancer tissue cell Metastatic tumor 1 A tumor grows 2 Cancer 3 Cancer cells spread 4 Cancer cells from a single cells invade through lymph and may survive cancer cell. neighboring blood vessels to and establish tissue. other parts of the a new tumor body. in another part of the body.  Loss of Cell Cycle Controls in Cancer Cells Treatments for metastasizing cancers include high-energy radiation and chemotherapy with toxic drugs – target dividing cells Chemotherapeutic drugs interfere with specific steps in the cell cycle For example, Taxol prevents microtubule depolymerization, preventing cells from proceeding past metaphase. The side effects of chemotherapy are due to the drug’s effects on normal cells For example, nausea results from chemotherapy’s effects on intestinal cells, hair loss results from its effects on hair follicle cells, and susceptibility to infection results from its effects on immune system cells. Now know a great deal about cell signaling pathways and how their malfunction is involved in the development of cancer through effects on the cell cycle Coupled with new molecular techniques, such as the ability to rapidly sequence the DNA of cells in a particular tumor, medical treatments for cancer are beginning to become more “personalized” to each patient’s tumor