This Week 11/16 Mitosis overview Major Vocab and Steps 11/17 Regulation of the Cell Cycle 11/18 - Loss of Regulation Cancer 11/19 Chapter 9 Quiz 11/20 Steps of Mesiosis Bozeman video 28 Khan academy is high quality on this! 11/16 Today Mitosis Overview Prequiz 1.) Why Mitosis? 2.) Vocab 3.) Steps of Mitosisopicpage/p53-the-most- frequently-altered-gene-in Overview: 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 2014 Pearson Education, Inc. Figure 9.1 In unicellular organisms, division of one cell reproduces the entire organism Cell division enables multicellular eukaryotes to develop from a single cell and, once fully grown, to renew, repair, or replace cells as needed Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division 2014 Pearson Education, Inc. Figure 9.2 (a) Reproduction 100 m (c) Tissue renewal (b) Growth and development 200 m 20 m 2014 Pearson Education, Inc. Figure 9.2a (a) Reproduction 100 m 2014 Pearson Education, Inc. Figure 9.2b (b) Growth and development 200 m 2014 Pearson Education, Inc. Figure 9.2c (c) Tissue renewal 20 m Cellular Organization of the Genetic Material Genome Chromosomes Chromatin Sister Chromatid Centriole 2014 Pearson Education, Inc. Kinetochore Somatic Cell Microtubule Aster Centrosome 2014 Pearson Education, Inc. Figure 9.3 Eukaryotic chromosomes 20 m Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein 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 one set of chromosomes 2014 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 identical copies of the original chromosome The centromere is where the two chromatids are most closely attached 2014 Pearson Education, Inc. Figure 9.4 Centromere 0.5 m Sister chromatids During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei Once separate, the chromatids are called chromosomes 2014 Pearson Education, Inc. Figure Centromere Chromosomal DNA molecules Chromosomes Chromosome arm 1 2014 Pearson Education, Inc. Figure Centromere Sister chromatids Chromosomal DNA molecules Chromosomes Chromosome arm Chromosome duplication 1 2 2014 Pearson Education, Inc. Figure Centromere Sister chromatids Separation of sister chromatids Chromosomal DNA molecules Chromosomes Chromosome arm Chromosome duplication 1 3 2 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 nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell 2014 Pearson Education, Inc. Concept 9.2: 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 2014 Pearson Education, Inc. Phases of the Cell Cycle The cell cycle consists of Mitotic (M) phase, including mitosis and cytokinesis Interphase, including cell growth and copying of chromosomes in preparation for cell division 2014 Pearson Education, Inc. Interphase (about 90% of the cell cycle) can be divided into subphases G 1 phase (first gap) S phase (synthesis) G 2 phase (second gap) The cell grows during all three phases, but chromosomes are duplicated only during the S phase 2014 Pearson Education, Inc. Figure 9.6 Cytokinesis Mitosis S (DNA synthesis) G1G1 G2G2 Mitosis is conventionally divided into five phases Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis overlaps the latter stages of mitosis 2014 Pearson Education, Inc. Video: Animal Mitosis Video: Microtubules Mitosis Animation: Mitosis Video: Microtubules Anaphase Video: Nuclear Envelope 2014 Pearson Education, Inc. Figure 9.7a Centrosomes (with centriole pairs) G 2 of InterphaseProphasePrometaphase Chromosomes (duplicated, uncondensed) Early mitotic spindle Centromere Aster Fragments of nuclear envelope Nonkinetochore microtubules Kinetochore microtubule Kinetochore Nucleolus Plasma membrane Two sister chromatids of one chromosome Nuclear envelope 10 m 2014 Pearson Education, Inc. Figure 9.7b Metaphase Anaphase Telophase and Cytokinesis Cleavage furrow Nucleolus forming Nuclear envelope forming Spindle Centrosome at one spindle pole Daughter chromosomes 10 m Metaphase plate 2014 Pearson Education, Inc. Figure 9.7c Centrosomes (with centriole pairs) G 2 of InterphaseProphase Chromosomes (duplicated, uncondensed) Early mitotic spindle Centromere Aster Nucleolus Plasma membrane Two sister chromatids of one chromosome Nuclear envelope 2014 Pearson Education, Inc. Figure 9.7d Prometaphase Fragments of nuclear envelope Nonkinetochore microtubules Kinetochore microtubule Kinetochore Spindle Centrosome at one spindle pole Metaphase plate Metaphase 2014 Pearson Education, Inc. Figure 9.7e Anaphase Telophase and Cytokinesis Cleavage furrow Nucleolus forming Nuclear envelope forming Daughter chromosomes 2014 Pearson Education, Inc. Figure 9.7f G 2 of Interphase 10 m 2014 Pearson Education, Inc. Figure 9.7g Prophase 10 m 2014 Pearson Education, Inc. Figure 9.7h Prometaphase 10 m 2014 Pearson Education, Inc. Figure 9.7i 10 m Metaphase 2014 Pearson Education, Inc. Figure 9.7j Anaphase 10 m 2014 Pearson Education, Inc. Figure 9.7k Telophase and Cytokinesis 10 m The Mitotic Spindle: A Closer Look The mitotic spindle is a structure made of microtubules and associated proteins It controls chromosome movement during mitosis In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center 2014 Pearson Education, Inc. The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase An aster (radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters 2014 Pearson Education, Inc. During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes Kinetochores are protein complexes that assemble on sections of DNA at centromeres At metaphase, the centromeres of all the chromosomes are at the metaphase plate, an imaginary structure at the midway point between the spindles two poles 2014 Pearson Education, Inc. Video: Mitosis Spindle 2014 Pearson Education, Inc. Figure 9.8 Metaphase plate (imaginary) Chromosomes Aster Kinetochore microtubules Kineto- chores Sister chromatids 1 m Centrosome Overlapping nonkinetochore microtubules Centrosome Microtubules 0.5 m 2014 Pearson Education, Inc. Figure 9.8a Chromosomes 1 m Centrosome Microtubules 2014 Pearson Education, Inc. Figure 9.8b Kinetochore microtubules Kinetochores 0.5 m 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 Chromosomes are also reeled in by motor proteins at spindle poles, and microtubules depolymerize after they pass by the motor proteins 2014 Pearson Education, Inc. 11/17 Regulating the Cell Cycle .)Cleavage Furrows .)Regulation at Different Steps .) CDK .) p53 2014 Pearson Education, Inc. Figure 9.9 Kinetochore Experiment Spindle pole Results Kinetochore Conclusion Mark Tubulin subunits Chromosome Motor protein Chromosome movement Microtubule 2014 Pearson Education, Inc. Figure 9.9a Kinetochore Experiment Spindle pole Mark 2014 Pearson Education, Inc. Figure 9.9b Results Kinetochore Conclusion Tubulin subunits Chromosome Motor protein Chromosome movement Microtubule 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 2014 Pearson Education, Inc. Animation: Cytokinesis Video: Cytokinesis and Myosin 2014 Pearson Education, Inc. Figure 9.10 (a) Cleavage of an animal cell (SEM) New cell wall Contractile ring of microfilaments Cleavage furrow Daughter cells Cell plate Wall of parent cell Vesicles forming cell plate 100 m 1 m (b) Cell plate formation in a plant cell (TEM) 2014 Pearson Education, Inc. Figure 9.10a (a) Cleavage of an animal cell (SEM) Contractile ring of microfilaments Cleavage furrow Daughter cells 100 m 2014 Pearson Education, Inc. Figure 9.10aa Cleavage furrow 100 m 2014 Pearson Education, Inc. Figure 9.10b New cell wall Daughter cells Cell plate Wall of parent cell Vesicles forming cell plate 1 m (b) Cell plate formation in a plant cell (TEM) 2014 Pearson Education, Inc. Figure 9.10ba Wall of parent cell Vesicles forming cell plate 1 m 2014 Pearson Education, Inc. Figure m Nucleus Telophase Nucleolus Chromosomes condensing Chromosomes Prometaphase Cell plate Prophase AnaphaseMetaphase 2014 Pearson Education, Inc. Figure 9.11a 10 m Nucleus Nucleolus Chromosomes condensing Prophase 1 2014 Pearson Education, Inc. Figure 9.11b 10 m 2 Prometaphase Chromosomes 2014 Pearson Education, Inc. Figure 9.11c 10 m 3 Metaphase 2014 Pearson Education, Inc. Figure 9.11d 10 m 4 Anaphase 2014 Pearson Education, Inc. Figure 9.11e 10 m 5 Telophase Cell plate Binary Fission in Bacteria Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission In E. coli, the single chromosome replicates, beginning at the origin of replication The two daughter chromosomes actively move apart while the cell elongates The plasma membrane pinches inward, dividing the cell into two 2014 Pearson Education, Inc. Figure Origin of replication Two copies of origin Bacterial chromosome Plasma membrane Cell wall E. coli cell Chromosome replication begins. 2014 Pearson Education, Inc. Figure Origin of replication Two copies of origin Bacterial chromosome Plasma membrane Cell wall E. coli cell Origin Chromosome replication begins. 2 One copy of the origin is now at each end of the cell. 2014 Pearson Education, Inc. Figure Origin of replication Two copies of origin Bacterial chromosome Plasma membrane Cell wall E. coli cell Origin Chromosome replication begins. 2 3 One copy of the origin is now at each end of the cell. Replication finishes. 2014 Pearson Education, Inc. Figure Origin of replication Two copies of origin Bacterial chromosome Plasma membrane Cell wall E. coli cell Origin Chromosome replication begins One copy of the origin is now at each end of the cell. Replication finishes. Two daughter cells result. The Evolution of Mitosis Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission Certain protists (dinoflagellates, diatoms, and some yeasts) exhibit types of cell division that seem intermediate between binary fission and mitosis 2014 Pearson Education, Inc. Figure 9.13 Chromosomes Intact nuclear envelope Microtubules Kinetochore microtubule Intact nuclear envelope (a) Dinoflagellates (b) Diatoms and some yeasts 2014 Pearson Education, Inc. A. What would you expect to happen if you fuse a cell in S with a cell in G 1 ? Why? B. What would you expect to happen to a nucleus from a G 1 cell if it is introduced into an enucleated M cell? Why? 2014 Pearson Education, Inc. Figure 9.14 G 1 nucleus immediately entered S phase and DNA was synthesized. Experiment Experiment 1 Experiment 2 Results S S S M G1G1 M M G1G1 G 1 nucleus began mitosis without chromosome duplication. Conclusion Molecules present in the cytoplasm control the progression to S and M phases. Checkpoints of 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 timing device of a washing machine 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 2014 Pearson Education, Inc. Figure 9.15 M checkpoint S M G1G1 G2G2 G 1 checkpoint G 2 checkpoint Control system For many cells, the G 1 checkpoint seems to be the most important If a cell receives a go-ahead signal at the G 1 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 G 0 phase 2014 Pearson Education, Inc. Figure 9.16 M checkpoint G1G1 G 1 checkpoint M G1G1 G2G2 Without go-ahead signal, cell enters G 0. G0G0 With go-ahead signal, cell continues cell cycle. (a) G 1 checkpoint Prometaphase G1G1 M G2G2 Without full chromosome attachment, stop signal is received. (b) M checkpoint S G1G1 M G1G1 G2G2 G 2 checkpoint Metaphase Anaphase With full chromosome attachment, go-ahead signal is received. 2014 Pearson Education, Inc. Figure 9.16a G1G1 G 1 checkpoint Without go-ahead signal, cell enters G 0. G0G0 With go-ahead signal, cell continues cell cycle. (a) G 1 checkpoint G1G1 2014 Pearson Education, Inc. Figure 9.16b M checkpoint M G1G1 G2G2 Prometaphase Without full chromosome attachment, stop signal is received. (b) M checkpoint M G1G1 G2G2 G 2 checkpoint Metaphase Anaphase With full chromosome attachment, go-ahead signal is received. The cell cycle is regulated by a set of regulatory proteins and protein complexes including kinases and proteins called cyclins 2014 Pearson Education, Inc. An example of an internal signal occurs at the M phase checkpoint In this case, anaphase does not begin if any kinetochores remain unattached to spindle microtubules Attachment of all of the kinetochores activates a regulatory complex, which then activates the enzyme separase Separase allows sister chromatids to separate, triggering the onset of anaphase 2014 Pearson Education, Inc. 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 2014 Pearson Education, Inc. Figure A sample of human connective tissue is cut up into small pieces. Petri dish Scalpels 2014 Pearson Education, Inc. Figure A sample of human connective tissue is cut up into small pieces. 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Petri dish Scalpels 2014 Pearson Education, Inc. Figure A sample of human connective tissue is cut up into small pieces. 2 3 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Cells are transferred to culture vessels. Petri dish Scalpels 4 PDGF is added to half the vessels. 2014 Pearson Education, Inc. Figure A sample of human connective tissue is cut up into small pieces Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Cells are transferred to culture vessels. PDGF is added to half the vessels. Without PDGF With PDGF Cultured fibroblasts (SEM) 10 m Petri dish Scalpels 2014 Pearson Education, Inc. Figure 9.17a Cultured fibroblasts (SEM) 10 m Another example of external signals is density- dependent inhibition, Most animal cells also exhibit anchorage dependence Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence 2014 Pearson Education, Inc. Characteristics of Cancer Tumors multiple layers of disorganized cells NEOPLASIA: invade and destroy Benign tumor: encapsulated Malignant tumor: metastasizes (spreads) Characteristics of Cancer NO contact inhibition Characteristics of Cancer Angiogenesis release a growth factor that caused nearby blood vessels to grow and bring more nutrients and oxygen to the tumor. 2014 Pearson Education, Inc. Figure 9.18 Anchorage dependence: cells require a surface for division 20 m Density-dependent inhibition: cells divide to fill a gap and then stop Density-dependent inhibition: cells form a single layer 20 m (a) Normal mammalian cells (b) Cancer cells 2014 Pearson Education, Inc. Figure 9.18a 20 m (a) Normal mammalian cells 2014 Pearson Education, Inc. Figure 9.18b (b) Cancer cells 20 m Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond to signals that normally regulate the cell cycle Cancer cells may not need growth factors to grow and divide They may make their own growth factor They may convey a growth factors signal without the presence of the growth factor They may have an abnormal cell cycle control system 2014 Pearson Education, Inc. A normal cell is converted to a cancerous cell by a process called 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 the original site, the lump is called a benign tumor Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors 2014 Pearson Education, Inc. Figure A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may metastasize to another part of the body. Breast cancer cell (colorized SEM) Lymph vessel Blood vessel Cancer cell Metastatic tumor Glandular tissue Tumor 5 m 2 3 4 2014 Pearson Education, Inc. Figure 9.19a A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. Glandular tissue Tumor 1 23 2014 Pearson Education, Inc. Figure 9.19b 43 Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may metastasize to another part of the body. Lymph vessel Blood vessel Cancer cell Metastatic tumor 2014 Pearson Education, Inc. Figure 9.19c Breast cancer cell (colorized SEM) 5 m 2014 Pearson Education, Inc. Figure 9.UN01 Control Treated A B C Amount of fluorescence per cell (fluorescence units) Number of cells 2014 Pearson Education, Inc. Figure 9.UN02 S G1G1 G2G2 Mitosis Telophase and Cytokinesis MITOTIC (M) PHASE Anaphase Metaphase Prometaphase Prophase 2014 Pearson Education, Inc. Figure 9.UN03