The Cell Cycle - Chapter 12 PDF

Chapter 12 The Cell Cycle Lecture Presentations by Nicole Tunbridge and © 2017 Pearson Education, Inc. Kathleen Fitzpatrick The Key Roles o...

Chapter 12 The Cell Cycle Lecture Presentations by Nicole Tunbridge and © 2017 Pearson Education, Inc. Kathleen Fitzpatrick The 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 © 2017 Pearson Education, Inc. Figure 12.1 © 2017 Pearson Education, Inc. Figure 12.1a Chromosomes (blue) are attached by specific proteins (green) to cell machinery (red) and are moved during division of a rat kangaroo cell. © 2017 Pearson Education, Inc.  In unicellular organisms, division of one cell reproduces the entire organism  Multicellular eukaryotes depend on cell division for  development from a fertilized egg  growth  repair  Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division © 2017 Pearson Education, Inc. Figure 12.2 100 µm (a) Asexual reproduction 50 µm (b) Growth and development (c) Tissue renewal 20 µm © 2017 Pearson Education, Inc. Concept 12.1: Most cell division results in genetically identical daughter cells  Most cell division results in two daughter cells with identical genetic information, DNA  The exception is meiosis, a special type of division that can produce sperm and egg cells © 2017 Pearson Education, Inc. 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 © 2017 Pearson Education, Inc. Figure 12.3 20 µm © 2017 Pearson Education, Inc.  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 © 2017 Pearson Education, Inc. 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 (joined copies of the original chromosome), attached along their lengths by cohesins  The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached © 2017 Pearson Education, Inc. Figure 12.4 Sister chromatids Centromeres, one on each sister chromatid 0.5 µm © 2017 Pearson Education, Inc.  During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei  Once separate, the chromatids are called chromosomes © 2017 Pearson Education, Inc. Figure 12.5_3 1 Chromosomes Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication 2 Sister chromatids Separation of sister chromatids 3 © 2017 Pearson Education, Inc.  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 cell division called meiosis  Meiosis yields non-identical daughter cells that have half as many chromosomes as the parent cell © 2017 Pearson Education, Inc. Concept 12.2: The mitotic phase alternates with interphase in the cell cycle  In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis © 2017 Pearson Education, Inc. 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) © 2017 Pearson Education, Inc.  Interphase (about 90% of the cell cycle) can be divided into three phases:  G1 phase (“first gap”)- growth + development****  S phase (“synthesis”)- replicates DNA***** NOTE- now there is more DNA present…*****  G2 phase (“second gap”)  The cell grows during all three phases, but chromosomes are duplicated only during the S phase © 2017 Pearson Education, Inc. Figure 12.6 G1 S (DNA synthesis) sis e k in G2 is o yt s ito C M © 2017 Pearson Education, Inc.  Mitosis is conventionally broken down into five stages:  prophase  prometaphase  metaphase  anaphase  telophase © 2017 Pearson Education, Inc. Figure 12.7a 10 µm G2 of Interphase Prophase Prometaphase Centrosomes Chromosomes Early mitotic Fragments Nonkinetochore (with centriole (duplicated, Aster of nuclear spindle microtubules pairs) uncondensed) Centromere envelope Plasma Nucleolus Two sister chromatids Kinetochore Kinetochore Nuclear membrane of one chromosome microtubules envelope © 2017 Pearson Education, Inc. Figure 12.7b 10 µm Metaphase Anaphase Telophase and Cytokinesis Metaphase Cleavage Nucleolus plate furrow forming Daughter chromosomes Spindle Nuclear Centrosome at envelope one spindle pole forming © 2017 Pearson Education, Inc. The Mitotic Spindle: A Closer Look  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(surrounding centrioles) that migrate to opposite ends of the cell beginning in prophase*********** © 2017 Pearson Education, Inc.  An aster (a radial array of short microtubules) extends from each centrosome  The spindle includes the centrosomes, the spindle microtubules, and the asters  During prophase, the nuclear envelope has to disappear in order for the microtubules to start attaching to the kinetochores.******* © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc.  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(equator), a plane midway between the spindle’s two poles***** © 2017 Pearson Education, Inc. Figure 12.8 Aster Centrosome Sister chromatids Metaphase plate (imaginary) Kineto- chores Microtubules Overlapping nonkinetochore microtubules Kinetochore microtubules Chromosomes Centrosome 1 µm 0.5 µm © 2017 Pearson Education, Inc.  In anaphase the cohesins are cleaved by an enzyme called separase*****  The kinetochore microtubules start to shorten and begin pulling at the centromeres****  Sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell*****  They are now referred to as chromosomes.*******  The microtubules shorten by depolymerizing at their kinetochore ends © 2017 Pearson Education, Inc.  Results of a clever experiment suggest that motor proteins on kinetochores “walk” the chromosomes along the microtubules during anaphase  The depolymerization***** of the microtubules(or deconstruction of the mitotic spindle) at the kinetochore ends occurs after the motor proteins have passed************  This is called the “Pac-man” mechanism  Bioflix- https:// www.youtube.com/watch?v=IvJrDsRuWxQ  2:43 © 2017 Pearson Education, Inc. Figure 12.9b Results Conclusion Chromosome movement Kinetochore Motor Tubulin Microtubule protein subunits Chromosome Data from G. J. Gorbsky, P. J. Sammak, and G. G. Borisy, Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends, Journal of Cell Biology 104:9–18 (1987). © 2017 Pearson Education, Inc.  Non-kinetochore microtubules from opposite poles overlap and push against each other, elongating the cell  At the end of anaphase, duplicate groups of chromosomes have arrived at opposite ends of the elongated cell  Cytokinesis begins during anaphase or telophase, and the spindle eventually disassembles  During telophase 2 new nuclei form, the spindles shorten and disappear and the chromosomes unravel into chromatin.****** © 2017 Pearson Education, Inc.  Review of Mitosis/Cell Division  https:// www.bozemanscience.com/028-cell-cycle-mitosis-a nd-meiosis  https:// static1.squarespace.com/static/50d5cc57e4b0e383f 5b1eb34/t/53ea46a1e4b0a0612515a56f/14078624 33641/AP+Bio-028+Cell+Cycle%2C+Mitosis+and+ Meiosis+Worksheet-WL.pdf © 2017 Pearson Education, Inc. Cytokinesis: A Closer Look  In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow  In plant cells, a cell plate forms during cytokinesis***  The cell plate is formed from cell wall building blocks.****** © 2017 Pearson Education, Inc. Figure 12.10 (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM) Cleavage furrow 100 µm Vesicles Wall of parent cell 1 µm forming New cell cell plate Cell plate wall Contractile ring of Daughter cells microfilaments Daughter cells © 2017 Pearson Education, Inc. Figure 12.11 Nucleus Chromosomes Nucleolus condensing Chromosomes 10 µm 1 Prophase 2 Prometaphase Cell plate 3 Metaphase 4 Anaphase 5 Telophase © 2017 Pearson Education, Inc. Binary Fission- 2:19 https://www.youtube.com/watch?v=u5UyBrgVsvs © 2017 Pearson Education, Inc. 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 © 2017 Pearson Education, Inc. Figure 12.12_4 Origin of Cell wall replication Plasma membrane Bacterial cell Bacterial 1 Chromosome replication Two copies chromosome begins. of origin Origin Origin 2 One copy of the origin is now at each end of the cell. 3 Replication finishes. 4 Two daughter cells result. © 2017 Pearson Education, Inc. The Evolution of Mitosis  Because 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  Chromosomes are segregated by the mitotic spindle, but the nuclear envelope remains intact during division. See (b) and (c) on next slide!! ***** © 2017 Pearson Education, Inc. Figure 12.13 Bacterial Kinetochore chromosome microtubule Intact nuclear envelope (a) Bacteria (c) Diatoms and some yeasts Chromosomes Kinetochore Microtubules microtubule Intact nuclear Fragments of envelope nuclear envelope (b) Dinoflagellates (d) Most eukaryotes © 2017 Pearson Education, Inc. Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system  The frequency of cell division varies with the type of cell  These differences result from regulation at the molecular level  Cancer cells manage to escape the usual controls on the cell cycle © 2017 Pearson Education, Inc. The Cell Cycle Control System  The cell cycle appears to be driven by specific chemical signals present in the cytoplasm.  Some evidence for this hypothesis comes from experiments at the University of Colorado in which they induced cultured mammalian cells at different phases of the cell cycle to fuse to form a single cell with two nuclei. © 2017 Pearson Education, Inc. In Experiment 1- When a cell in S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase and DNA was synthesized. In Experiment 2-When a cell in M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis- a spindle formed and the chromosomes condensed, even though chromosomes had not been duplicated. Conclusion- The result of fusing G1 cell with a cell in the S or M phase of the cell cycle suggest that molecules present in the cytoplasm during S or M phases control the progression TO those phases. Figure 12.14 Experiment Experiment 1 Experiment 2 S G1 M G1 Results S S M M G1 nucleus G1 nucleus began immediately entered mitosis without S phase and DNA chromosome was synthesized. duplication. Conclusion Molecules present in the cytoplasm control the progression to S and M phases. Data from R. T. Johnson and P. N. Rao, Mammalian cell fusion: Induction of premature chromosome condensation in interphase nuclei, Nature 226:717–722 (1970). © 2017 Pearson Education, Inc.  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 © 2017 Pearson Education, Inc. Figure 12.15 G1 checkpoint Control G1 system S M G2 M checkpoint G2 checkpoint © 2017 Pearson Education, Inc.  Intro and Review Video-Cell Cycle Control https://www.youtube.com/watch?v=YADEzvudGRQ 4:42 The Cell Cycle Clock: Cyclins and Cyclin- Dependent Kinases  Two types of regulatory proteins are involved in cell cycle control: 1) cyclins 2) cyclin-dependent kinases (Cdks)  The activity of a Cdk rises and falls with changes in concentration of its cyclin partner******  MPF (maturation-promoting factor) IS a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase. ******  Read over diagram of next page ****** © 2017 Pearson Education, Inc. Figure 12.16 1 S G M G1 S G2 M G1 S G2 M G1 Cdk MPF Cyclin M activity concentration Degraded G2 cyclin Cdk Cyclin is degraded MPF Cyclin Time G2 checkpoint (a) Fluctuation of MPF activity and cyclin (b) Molecular mechanisms that help concentration during the cell cycle regulate the cell cycle © 2017 Pearson Education, Inc. Stop and Go Signs: Internal and External Signals at the Checkpoints  Many signals registered at checkpoints come from cellular surveillance mechanisms within the cell  Checkpoints also register signals from outside the cell  Three important checkpoints are those in the G1, G2, and M phases © 2017 Pearson Education, Inc.  For many cells, the G1 checkpoint seems to be the most important!  If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, 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. Therefore no additional time will be spent in the cell cycle.******** © 2017 Pearson Education, Inc.  Most cells of the human body are actually in the G0 phase.*******  Mature nerve cells and muscle cells never divide.  Other cells, such as liver cells, can be “called back” from the G0 phase to the cell cycle by external cues, such as growth factors released during injury.  Read over next slide diagram******* © 2017 Pearson Education, Inc. Figure 12.17 G1 checkpoint G0 G1 G1 Without go-ahead signal, cell With go-ahead signal, cell G1 enters G0. continues cell cycle. S (a) G1 checkpoint M G2 G1 G1 M G2 M G2 M checkpoint G2 Anaphase checkpoint Prometaphase Metaphase Without full chromosome attachment, With full chromosome stop signal is received. attachment, go-ahead signal is received. (b) M checkpoint © 2017 Pearson Education, Inc.  An example of an internal signal is that cells will not begin anaphase until all chromosomes are properly attached to the spindle at the metaphase plate  This mechanism ensures that daughter cells have the correct number of chromosomes © 2017 Pearson Education, Inc. What are the stop and go ahead signals that control cell division- 1) Anchorage Dependence- there must be a surface or substratum to divide. 2) Density-Dependent Inhibition- if too crowded, too many cells, cell division stops. 3) Growth Factors- proteins that stimulate cell division. If not present, no cell division occurs. Review- Cell Cycle Control- Nucleus Biology https://www.youtube.com/watch?v=e6N9_RhD10Q 3:43 Loss of Cell Cycle Controls(signals) in Cancer Cells  Cancer cells do not respond normally to the body’s control mechanisms like density-dependent inhibition or anchorage dependence. Therefore tumors can be formed.**********  Cancer cells do 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 © 2017 Pearson Education, Inc.  Cancer cells acquire the ability to divide indefinitely(immortal) and are undergoing transformation  Ex. HeLa cells- taken from a cancerous tumor in 1951 that are still being cultured today https://www.youtube.com/watch?v=auLZn1e3WwA  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 the original site, the lump is called a benign tumor © 2017 Pearson Education, Inc.  Malignant tumors invade surrounding tissues and can undergo metastasis, the spread of cancer cells to other parts of the body, where they may form additional tumors  Localized tumors may be treated with high-energy radiation, which damages the DNA in the cancer cells  To treat metastatic cancers, chemotherapies that target the cell cycle may be used © 2017 Pearson Education, Inc. Figure 12.20 5 µm Breast cancer cell (colorized SEM) Metastatic Lymph tumor vessel Tumor Blood vessel Glandular Cancer tissue cell 1 A tumor grows 2 Cancer cells invade 3 Cancer cells spread 4 A small percentage from a single neighboring tissue. through lymph and of cancer cells may cancer cell. blood vessels to other metastasize to parts of the body. another part of the body. © 2017 Pearson Education, Inc.  Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment  Coupled with the ability to sequence the DNA of cells in a particular tumor, treatments are becoming more “personalized”. © 2017 Pearson Education, Inc. For example- the drug Taxol  This drug freezes the mitotic spindle by preventing microtubule depolymerization, which stops actively dividing cells from proceeding past metaphase and leads to their destruction. *******  Taxol- Paclitaxel, the most well-known natural-source cancer drug in the United States, is derived from the bark of the Pacific yew tree (Taxus brevifolia) and is used in the treatment of cancers of the breast, lung, ovary, cervix, pancreas, as well as Kaposi's sarcoma.  It is administered by intravenous injection. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. © 2017 Pearson Education, Inc. Dogs Can Smell Cancer (BBC) https://www.youtube.com/watch?v=ijstvRYqKpc 15:04