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• The Cell Cycle Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pre-Unit Questions • What types of cells undergo mitosis? • What is a haploid cell? – Give an example of this type of cell • What is a diploid cell? – Give an example of this type of cell • True or False – the cell cycle consists of prophase, metaphase, anaphase, and telophase only. (if false, correct the statement) • What are the parts of a duplicated chromosome • Can you identify the following stages of mitosis Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Cell Cycle • Overview: The Key Roles of Cell Division • The continuity of life – Is based upon the reproduction of cells, or cell division 100 µm • Unicellular organisms – Reproduce by cell division (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual Figure 12.2 A organism (LM). Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Division • Multicellular organisms depend on cell division for – Development from a fertilized cell – Growth – Repair 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 give rise to new blood cells (LM). after the fertilized egg divided, Figure 12.2 B, C forming two cells (LM). Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Division • Cell division 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cellular Organization of the Genetic Material • A cell’s endowment of DNA, its genetic information – Is called its genome Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Material • The DNA molecules in a cell – Are packaged into chromosomes Figure 12.3 50 µm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Material • Eukaryotic chromosomes – Consist of chromatin, a complex of DNA and protein that condenses during cell division Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Distribution of Chromosomes During Cell Division • In animals – Somatic cells have two sets of chromosomes • diploid – Sex cells (gametes) have one set of chromosomes • haploid • In preparation for cell division – DNA is replicated and the chromosomes condense Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phases of the Cell Cycle • The cell cycle consists of – The mitotic phase – Interphase – the cell grows, duplicates proteins, organelles and chromosomes INTERPHASE The mitotic phase alternates with interphase G1 S (DNA synthesis) G2 Figure 12.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interphase – and its subphases (preparation for cell division) G1 phase – cell grows, produces proteins and organelles requires structural proteins and enzymes S phase – DNA synthesis (form sister chromatids) (see next slide) G2 phase – 2nd growth phase. During G2, organelles replicate, chromosomes get ready to condense, and microtubules start to form at centrioles. INTERPHASE M phase –cell division and cytokinesis G1 Mitosis – division of the nucleus S (DNA synthesis) G2 Cytokinesis – division of the cytoplasm Figure 12.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Duplicated Chromosomes • 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. Figure 12.4 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Centromeres Sister chromatids Sister chromatids The Mitotic Phase – Mitosis and Cytokinesis • Mitosis consists of five distinct phases – Prophase – Prometaphase G2 OF INTERPHASE Centrosomes Chromatin (with centriole pairs) (duplicated) Figure 12.6 Nucleolus Nuclear Plasma envelope membrane PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PROMETAPHASE Fragments Kinetochore of nuclear envelope Nonkinetochore microtubules Kinetochore microtubule Mitosis – Metaphase – Anaphase – Telophase METAPHASE ANAPHASE Metaphase plate Figure 12.6 Spindle Centrosome at Daughter one spindle pole chromosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings TELOPHASE AND CYTOKINESIS Cleavage furrow Nuclear envelope forming Nucleolus forming The Mitotic Spindle: A Closer Look • The mitotic spindle – Is an apparatus of microtubules that controls chromosome movement during mitosis Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The mitotic spindle • The spindle arises from the centrosomes – And includes spindle microtubules and asters – Within an animal cell centrosome there is a pair of small organelles, the centrioles – Unlike centrosomes in animal cells, plant cells do not have centrioles. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic spindle • An aster is an array of microtubules that has formed from the centrosome after it moves to opposite poles. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic spindle • Some spindle microtubules – Attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate Aster Kinetochore microtubules attach to the kinetochore and the poles. These fibers will then attach to the mitotic spindle fibers which will move the sister chromatids towards the opposite poles Sister chromatids Centrosome Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules Microtubules 0.5 µm Figure 12.7 Centrosome 1 µm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chromosomes Mitotic spindle • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Moving chromosomes • In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell – Nonkinetechore microtubules from opposite poles overlap and push against each other, elongating the cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Movement of chromosomes • In telophase – Genetically identical daughter nuclei form at opposite ends of the cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis Review • Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis: A Closer Look • In animal cells – Cytokinesis occurs by a process known as cleavage, forming a cleavage furrow Cleavage furrow Contractile ring of microfilaments Figure 12.9 A 100 µm Daughter cells (a) Cleavage of an animal cell (SEM) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis • In plant cells, during cytokinesis – A cell plate forms Vesicles forming cell plate 1 µm Wall of patent cell Cell plate New cell wall Daughter cells Figure 12.9 B (b) Cell plate formation in a plant cell (SEM) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of Mitosis • Mitosis in a plant cell Chromatine Nucleus Nucleolus condensing Chromosome Metaphase. The 2 Prometaphase. 3 1 Prophase. spindle is complete, 4 The chromatin We now see discrete and the chromosomes, is condensing. chromosomes; each attached to microtubules The nucleolus is consists of two at their kinetochores, beginning to identical sister are all at the metaphase disappear. chromatids. Later plate. Although not in prometaphase, the yet visible nuclear envelop will in the micrograph, fragment. the mitotic spindle is staring to from. Figure 12.10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Anaphase. The 5 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. Binary Fission • Prokaryotes (bacteria) – Reproduce by a type of cell division called binary fission – Results in two genetically identical cells Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Binary Fission • In binary fission – The bacterial chromosome replicates. • Begins at the origin of replication – The two daughter chromosomes actively move apart Origin of replication 1 Origin of replication opens up like a bubble and the two strands move in opposite directions 2 Replication continues until one copy of the origin is now at each end of the cell. 43 Each replicated strand attached itself to the cell membrane. The cell elongates, separating the replicated strands 4 The cell wall grows across the middle of the cell 5 Two daughter cells result. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings E. coli cell Two copies of origin Origin Cell wall Plasma Membrane Bacterial Chromos ome Origin The Evolution of Mitosis • Since prokaryotes preceded eukaryotes by billions of years – It is likely that mitosis evolved from bacterial cell division • mitosis is a universal eukaryotic property – All eukaryotes (except amoeba) undergo mitosis. • the key molecules involved in mitosis, have homologous moleclues in prokaryotes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Cycle Controls To grow and develop normally a plant or animal cell must be able to control the timing of cell division. • The frequency of cell division – Varies with the type of cell The events are directed by a cell cycle control system Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G1 phase checkpoint • The cell has a checkpoint at this phase. The cellular environment is checked and cell size. Only when conditions are right will the cell proceed into the S phase – If signal is not received it goes to a nondividing stage called G0 phase. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G0 Phase • This is mitotic dormancy or differentiation • Cells are not considered to be in the cycle of division but become differentiated or specialized in their function • Cells can “mature” at this time to play a role based on the specific genes they express. • Some cells remain here permanently. Some may stay here for hours, days, months. – E.g. nerve cells • Some can revert back to G1, S and G2 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other Checkpoints • Check points will also occur after the S phase and G2 phase. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulators • Internal Regulators – Regulate the timing inside the cell cycle, when the cell can proceed from one phase to the next. • Ex. G1 to S phase • External Regulators – Regulate timing external to the cell, like when it is necessary for cells to divide in general Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulation comes from protein signals Cyclins are a class of proteins that regulate the cell cycle • Two main types • Cyclin Dependent Protein Kinases (Cdks) • Cyclins Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclins • undergo a constant cycle of synthesis and degradation during cell division • cyclins act as an activating protein and bind to Cdks forming a cyclin-Cdk complex • This complex then acts as a signal to the cell to pass to the next cell cycle phase. Eventually, the cyclin degrades, deactivating the Cdk, thus signaling exit from a particular phase. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulation-Cyclin dependent kinases • Cdks – These are simply found within the cell, not synthesized – Only become active when bound with cyclins – A Cdks is an enzyme that adds negatively charged phosphate groups to other molecules in a process called phosphorylation. Through phosphorylation, Cdks signal the cell that it is ready to pass into the next stage of the cell cycle Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In General • The combinations of cyclins and cyclindependent kinases (CDKs) work together to phosphorylate (add phosphate) and activate (or inactivate) target proteins in the steps of the cell cycle. Different combinations determine which target protein will be affected Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What are some factors that keep normal cells in “check” • Growth Factors – A protein that stimulates other cells to divide Density – dependent inhibition - causes crowded cells to stop dividing (run out of nutritens) Anchorage dependence – in order to divide, cells must be attached to a substrate Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Loss of Cell Cycle Controls • Cells that do not respond normally to these controls. – Cancer cells – Exhibit neither density-dependent inhibition nor anchorage dependence Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Loss of Cell Cycle Controls in Cancer Cells • Cancer cells – Do not respond normally to the body’s control mechanisms – Form tumors – Benign tumors remain at the original site and are usually harmless. • An abnormal mass of essentially normal cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tumors • Malignant tumors invade surrounding tissues and can affect one or more organs. • The cells have undergone a transformation (no longer “normal”) Figure 12.19 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer • Cells from a malignant tumor may split off, and travel to new locations, where they can form new tumors. • The spread of cancer cells beyond their original site is called metastasis Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer Treatments • Treatments for cancer include: – Radiation • Causes Apoptosis – “programmed cell death” – Many cells will kill themselves for the betterment of the organisms • Like cells damaged by virus • Cells in the lining of the uterus – Chemotherapy Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What prevents normal cells from becoming tumor cells • Genetic damage or errors are often repaired • The tumor suppressor gene p53 gene – This gene stops a damaged cell just before the S phase so that it can be repaired. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings