Transcript Cell Cycle
The Cell Cycle and How Cells Divide 1 Phases of the Cell Cycle • The cell cycle consists of – Interphase – normal cell activity – The mitotic phase – cell divsion INTERPHASE Growth G1 (DNA synthesis) Growth G2 2 Functions of Cell Division 100 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). 200 µm 20 µm (b) Growth and development. (c) Tissue renewal. These dividing This micrograph shows a bone marrow cells (arrow) will sand dollar embryo shortly after give rise to new blood cells (LM). the fertilized egg divided, forming two cells (LM). 3 Cell Division • • • An integral part of the cell cycle Results in genetically identical daughter cells Cells duplicate their genetic material – Before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA 4 DNA • • Genetic information - genome Packaged into chromosomes Figure 12.3 50 µm 5 DNA And Chromosomes • • An average eukaryotic cell has about 1,000 times more DNA then an average prokaryotic cell. The DNA in a eukaryotic cell is organized into several linear chromosomes, whose organization is much more complex than the single, circular DNA molecule in a prokaryotic cell 6 DNA And Chromosomes Prokaryotes Structure Single, naked, circular DNA molecule; attached to 1 point on the inner surface of plasma membrane Location In an area of the cytoplasm called the nucleoid Eukaryotes Many linear chromosomes, each made of 1 DNA molecule joined with protein Inside a membranebound nucleus 7 Chromosomes • All eukaryotic cells store genetic information in chromosomes. – Most eukaryotes have between 10 and 50 chromosomes in their body cells. – Human cells have 46 chromosomes. – 23 nearly-identical pairs 8 Structure of Chromosomes • • • Chromosomes are composed of a complex of DNA and protein called chromatin that condenses during cell division DNA exists as a single, long, doublestranded fiber extending chromosome’s entire length. Each unduplicated chromosome contains one DNA molecule, which may be several inches long 9 Structure of Chromosomes Every 200 nucleotide pairs, the DNA wraps twice around a group of 8 histone proteins to form a nucleosome. Higher order coiling and supercoiling also help condense and package the chromatin inside the nucleus: 10 Structure of Chromosomes The degree of coiling can vary in different regions of the chromatin: Heterochromatin refers to highly coiled regions where genes aren’t expressed. Euchromatin refers to loosely coiled regions where genes can be expressed. 11 Structure of Chromosomes • • • Prior to cell division each chromosome duplicates itself. During this time, only the heterochromatin is visible, as dense granules inside the nucleus. There is also a dense area of RNA production called the nucleolus: 12 Karyotype • • • An ordered, visual representation of the chromosomes in a cell Chromosomes are photographed when they are highly condensed, then photos of the individual chromosomes are arranged in order of decreasing size: In humans each somatic cell has 46 chromosomes, made up of two sets, one set of chromosomes comes from each parent Pair of homologous chromosomes 5 µm Centromere Sister chromatids 13 Chromosomes • • • Non-homologous chromosomes – Look different – Control different traits Sex chromosomes – Are distinct from each other in their characteristics – Are represented as X and Y – Determine the sex of the individual, XX being female, XY being male In a diploid cell, the chromosomes occur in pairs. The 2 members of each pair are called homologous chromosomes or homologues. 14 Chromosomes • • • A diploid cell has two sets of each of its chromosomes A human has 46 chromosomes (2n = 46) In a cell in which DNA synthesis has occurred all the chromosomes are duplicated and thus each consists of two identical sister chromatids Maternal set of chromosomes (n = 3) 2n = 6 Paternal set of chromosomes (n = 3) Two sister chromatids of one replicated chromosome Centromere Two nonsister chromatids in a homologous pair Pair of homologous chromosomes (one from each set) 15 Homologues • Homologous chromosomes: • Look the same • Control the same traits • May code for different forms of each trait • Independent origin - each one was inherited from a different parent 16 Genes • • • Gene – a section of a DNA molecule that contains the code for making one polypeptide. Gene locus –the location of a gene along the length of a chromosome Alleles – genes that can occupy the same gene locus (on different chromosomes) Red eyes White eyes Short wings Long wings Tan body Tan body 17 Homologues • However, homologous chromosomes are not identical because they may code for different forms of each trait: Red eyes Short wings Tan body White eyes Long wings Tan body 18 Chromosome Duplication • • In preparation for cell division, DNA is replicated and the chromosomes condense Each duplicated chromosome has two sister chromatids, which separate during cell division 0.5 µm A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids 19 Centrometers Sister chromatids Chromosome Duplication • • Because of duplication, each condensed chromosome consists of 2 identical chromatids joined by a centromere. Each duplicated chromosome contains 2 identical DNA molecules (unless a mutation occurred), one in each chromatid: Non-sister chromatids Centromere Duplication Sister chromatids Two unduplicated chromosomes Sister chromatids Two duplicated chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 20 Structure of Chromosomes • • The centromere is a constricted region of the chromosome containing a specific DNA sequence, to which is bound 2 discs of protein called kinetochores. Kinetochores serve as points of attachment for microtubules that move the chromosomes during cell division: Metaphase chromosome Centromere region of chromosome Kinetochore Kinetochore microtubules Sister Chromatids 21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structure of Chromosomes – – Diploid - A cell possessing two copies of each chromosome (human body cells). Homologous chromosomes are made up of sister chromatids joined at the centromere. Haploid - A cell possessing a single copy of each chromosome (human sex cells). 22 Phases of the Cell Cycle • • • Interphase – G1 - primary growth – S - genome replicated – G2 - secondary growth M - mitosis C - cytokinesis 23 Interphase • • G1 - Cells undergo majority of growth S - Each chromosome replicates (Synthesizes) to produce sister chromatids – Attached at centromere – Contains attachment site (kinetochore) • G2 - Chromosomes condense - Assemble machinery for division such as centrioles 24 Mitosis Some haploid & diploid cells divide by mitosis. Each new cell receives one copy of every chromosome that was present in the original cell. Produces 2 new cells that are both genetically identical to the original cell. DNA duplication during interphase Mitosis Diploid Cell 25 Mitotic Division of an Animal Cell G2 OF INTERPHASE Centrosomes (with centriole pairs) Nucleolus Chromatin (duplicated) Nuclear Plasma envelope membrane PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids PROMETAPHASE Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule 26 Mitotic Division of an Animal Cell METAPHASE ANAPHASE Metaphase plate Spindle Centrosome at Daughter one spindle pole chromosomes TELOPHASE AND CYTOKINESIS Cleavage furrow Nucleolus forming Nuclear envelope forming 27 G2 of Interphase • A nuclear envelope bounds the nucleus. • The nucleus contains one or more nucleoli (singular, nucleolus). • Two centrosomes have formed by replication of a single centrosome. • In animal cells, each centrosome features two centrioles. • Chromosomes, duplicated during S phase, cannot be seen individually because they have not yet condensed. G2 OF INTERPHASE Centrosomes (with centriole pairs) Chromatin (duplicated) The light micrographs show dividing lung cells from a newt, which has 22 chromosomes in its somatic cells (chromosomes appear blue, microtubules green, intermediate filaments red). For simplicity, the drawings show only four chromosomes. Nucleolus Nuclear Plasma envelope membrane 28 Prophase • The chromatin fibers become more tightly coiled, condensing into discrete chromosomes observable with a light microscope. • The nucleoli disappear. • Each duplicated chromosome appears as two identical sister chromatids joined together. • The mitotic spindle begins to form. It is composed of the centrosomes and the microtubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosomes are called asters (“stars”). • The centrosomes move away from each other, apparently propelled by the lengthening microtubules between them. PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids 29 Metaphase • Metaphase is the longest stage of mitosis, lasting about 20 minutes. • The centrosomes are now at opposite ends of the cell. •The chromosomes convene on the metaphase plate, an imaginary plane that is equidistant between the spindle’s two poles. The chromosomes’ centromeres lie on the metaphase plate. • For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles. • The entire apparatus of microtubules is called the spindle because of its shape. METAPHASE Metaphase plate Spindle Centrosome at one spindle pole 30 The Mitotic Spindle • • • • • The spindle includes the centrosomes, the spindle microtubules, and the asters The apparatus of microtubules controls chromosome movement during mitosis The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell Assembly of spindle microtubules begins in the centrosome, the microtubule organizing center An aster (a radial array of short microtubules) extends from each centrosome 31 The Mitotic Spindle • Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate Aster Microtubules Sister chromatids Chromosomes Centrosome Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0.5 µm 32 The Mitotic Spindle • • In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell The microtubules shorten by depolymerizing at their kinetochore ends Chromosome movement Microtubule Motor protein Kinetochore Tubulin subunits Chromosome 33 Anaphase • Anaphase is the shortest stage of mitosis, lasting only a few minutes. • Anaphase begins when the two sister chromatids of each pair suddenly part. Each chromatid thus becomes a fullfledged chromosome. • The two liberated chromosomes begin moving toward opposite ends of the cell, as their kinetochore microtubules shorten. Because these microtubules are attached at the centromere region, the chromosomes move centromere first (at about 1 µm/min). • The cell elongates as the nonkinetochore microtubules lengthen. • By the end of anaphase, the two ends of the cell have equivalent—and complete—collections of chromosomes. ANAPHASE Daughter chromosomes 34 Telophase • Two daughter nuclei begin to form in the cell. • Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other portions of the endomembrane system. • The chromosomes become less condensed. • Mitosis, the division of one nucleus into two genetically identical nuclei, is now complete. TELOPHASE AND CYTOKINESIS Cleavage furrow Nucleolus forming Nuclear envelope forming 35 Mitosis in a plant cell Chromatine Nucleus Nucleolus condensing 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Chromosome Metaphase. The 2 Prometaphase. 3 4 spindle is complete, We now see discrete and the chromosomes, chromosomes; each attached to microtubules consists of two at their kinetochores, identical sister are all at the metaphase chromatids. Later plate. in prometaphase, the nuclear envelop will fragment. 5 Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 36 Cytokinesis • Cleavage of cell into two halves – Animal cells Constriction belt of actin filaments – Plant cells Cell plate – Fungi and protists Mitosis occurs within the nucleus 37 Cytokinesis In Animal And Plant Cells 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell plate Wall of patent cell 1 µm Cell plate New cell wall Daughter cells Daughter cells (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM) 38 39 Binary Fission • • 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 Cell wall Origin of replication Plasma membrane E. coli cell Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell. Bacterial chromosome Two copies of origin Origin Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result. 40 Prokaryote Cell Division - Binary Fission • • • • Replication begins at a specific site called the origin of replication and proceeds bidirectionally in a circle Cell elongates and the newly replicated DNA molecules are actively partitioned. The cytoplasm is divided by growth of a new membrane and septum. Produces 2 daughter cells which are genetically identical (unless a mutation occurred) to each other and to the original cell. Origin of replication Prokaryotic genome Replication of DNA Elongation of cell and partitioning of DNA Formation of new membrane and septum Inward growth of septum Cell pinches in two Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 41 The Evolution of Mitosis • • Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis Bacterial chromosome Prokaryotes Chromosomes Microtubules Dinoflagellates Intact nuclear envelope Kinetochore microtubules Intact nuclear envelope Diatoms Kinetochore microtubules Centrosome Most eukaryotes Fragments of nuclear envelope 42 Cell Cycle Control System • • • • The 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 Cell can be put on hold at specific checkpoints. 43 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 clock has specific checkpoints where the cell cycle stops until a goahead signal is received G1 checkpoint Control system S G1 M G2 M checkpoint Figure 12.14 G2 checkpoint 44 G1 checkpoint G0 G1 checkpoint G1 (a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle. G1 (b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. 45 “Go Ahead Signals” - Regulatory Proteins - Cyclins • • • • To pass each checkpoint, specific regulatory proteins called cyclins must bind to an enzyme called Cyclin-dependent kinase (Cdk). They are synthesized during the stage preceding that checkpoint The cyclin-Cdk complex then activates numerous proteins needed for the next stage of the cell cycle by phosphorylating them The cyclins are then quickly degraded during the stage following that checkpoint P Cyclin Cyclin-dependent kinase (Cdk) P Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 46 (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Relative Concentration Molecular control at the G2 checkpoint M-Phase Promoting Factor - MPF G1 S G2 M MPF activity G 1 S G2 M Cyclin Time (b) Molecular mechanisms that help regulate the cell cycle 1 Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates. 5 During G1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. Cdk Degraded Cyclin Cyclin is degraded 4 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase. G2 Cdk checkpoint MPF Cyclin 2 Accumulated cyclin molecules combine with recycled Cdk molecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis. 3 MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. 47 Stop and Go Signs: Internal and External Signals at the Checkpoints • • Internal - Cyclins and Cyclin-dependent kinases (Cdks) An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal to delays anaphase 48 Stop and Go Signs: Internal and External Signals at the Checkpoints • • Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide Growth Factors stimulate other cells to divide – – – In multicellular organisms, passage through cell cycle check points is stimulated by growth factors Over 50 different growth factors have been identified, and each one binds to a different cell surface receptor Each growing cell binds with growth factors that stimulate cell division 49 Growth Factors and the Cell Cycle • • When a growth factor binds to the cell surface receptor, this triggers an intracellular signaling cascade that activates regulatory proteins inside the nucleus. The activated nuclear regulatory proteins stimulate DNA to produce proteins (e.g. Cdk or cyclins) needed to pass through cell cycle checkpoints 50 External Growth Factors • • • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture Another example of external signals is 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 51 Cancer • • • • Loss of Cell Cycle Controls Cancer cells do not respond normally to the body’s control mechanisms They exhibit neither density-dependent inhibition nor anchorage dependence Form tumors Lymph vessel Tumor Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring tissue. Blood vessel Cancer cell 3 Cancer cells spread through lymph and blood vessels to other parts of the body. Metastatic Tumor 4 A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 52