Biology Sylvia S. Mader Michael Windelspecht Chapter 9 The Cell Cycle and Cellular Reproduction Lecture Outline See separate FlexArt PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. 1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1

Biology, 9th ed,Sylvia Mader Chapter 09 9.1 The Cell Cycle The Cell Cycle The cell cycle is an orderly set of stages from the first division to the time the resulting daughter cells divide Just prior to the next division: The cell grows larger The number of organelles doubles The DNA is replicated The two major stages of the cell cycle: Interphase (includes several stages) Mitotic Stage (includes mitosis and cytokinesis)

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interphase S (growth and DNA replication) G1 checkpoint Cell cycle main checkpoint. If DNA is damaged, apoptosis will occur. Otherwise, the cell is committed to divide when growth signals are present and nutrients are available. G1 G2 checkpoint Mitosis checkpoint. Mitosis will occur if DNA has replicated properly. Apoptosis will occur if the DNA is damaged and cannot be repaired. G2 (growth and final preparations for division) G1 (growth) G0 M G2 Cytokinesis elophase Prophase Anaphase Metaphase Late prophase T M M checkpoint Spindle assembly checkpoint. Mitosis will not continue if chromosomes are not properly aligned.

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle Interphase Most of the cell cycle is spent in interphase Cell performs its usual functions Time spent in interphase varies by cell type Nerve and muscle cells do not complete the cell cycle (remain in the G0 stage)

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle Interphase consists of: G1, S, and G2 phases G1 Phase: Recovery from previous division Cell doubles its organelles Cell grows in size Cell accumulates raw materials for DNA synthesis S Phase: DNA replication Proteins associated with DNA are synthesized Chromosomes enter with 1 chromatid each Chromosomes leave with 2 identical chromatids (sister chromatids) each G2 Phase: Between DNA replication and onset of mitosis Cell synthesizes proteins necessary for division

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle M (Mitotic) Stage Includes: Mitosis Nuclear division Daughter chromosomes are distributed by the mitotic spindle to two daughter nuclei Cytokinesis Division of the cytoplasm Results in two genetically identical daughter cells

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle The cell cycle is controlled by internal and external signals A signal is a molecule that either stimulates or inhibits a metabolic event. Internal signals Family of proteins called cyclins that increase and decrease as the cell cycle continues Without cyclins, the cell cycle stops at G1, M or G2 (checkpoints) Allows time for any damage to be repaired

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle Apoptosis is programmed cell death It involves a sequence of cellular events: fragmenting of the nucleus, blistering of the plasma membrane engulfing of cell fragments. Apoptosis is caused by enzymes called caspases. Mitosis and apoptosis are opposing forces Mitosis increases cell number Apoptosis decreases cell number

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle Apoptosis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. apoptotic cell blebs DNA fragment Cell rounds up, and nucleus collapses. Chromatin condenses, and nucleus fragments. Plasma membrane blisters, and blebs form. Cell fragments contain DNA fragments. cell fragment Courtesy Douglas R. Green/LaJolla Institute for Allergy and Immunology

Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle The Cell Cycle Apoptosis Cells harbor caspases that are kept in check by inhibitors Can be unleashed by internal or external signals Signal protein p53 Stops the cell cycle at G1 when DNA is damaged Initiates an attempt at DNA repair If successful, the cycle continues to mitosis If not, apoptosis is initiated

Regulation at the G1 Checkpoint Biology, 9th ed,Sylvia Mader Chapter 09 Regulation at the G1 Checkpoint The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CDK not present CDK present P E2F binds to DNA. P RB protein E2F RB protein E2F E2F DNA released E2F E2F not released phosphorylated RB cell cycle proteins a. no DNA damage breakdown of p53 p53 p53 binds to DNA. DNA damage P P P P DNA DNA phosphorylated p53 DNA repair proteins apoptosis b.

G1 phase G2 phase S phase G0 phase During which stage of the cell cycle is cell growth and replication of organelles most significant? G1 phase G2 phase S phase G0 phase

Yes the tendon will regrow, p53 signals will activate the G1 stage. An accident has injured your Achilles tendon (muscle). Would you expect this tendon to regrow? Why or why not? Yes the tendon will regrow, p53 signals will activate the G1 stage. Yes the tendon will regrow. It has been in an inactive stage (G0) to conserve nutrients and energy. Yes the tendon will regrow because it is living tissue. Yes the tendon will regrow provided proper signals are received by the cells

9.2 Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 9.2 Mitosis and Cytokinesis The Cell Cycle DNA is in very long threads Chromosomes Stretched out and intertwined between divisions DNA is associated with histones (proteins) DNA and histone proteins are collectively called chromatin Before mitosis begins: Chromatin condenses (coils) into distinctly visible chromosomes Each species has a characteristic chromosome number

Biology, 9th ed,Sylvia Mader Chapter 09 Diploid Chromosome Numbers of Some Eukaryotes The Cell Cycle

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle The diploid (2n) number includes two sets of chromosomes of each type Humans have 23 different types of chromosomes Each type is represented twice in each body cell (diploid) Only sperm and eggs have one of each type ·termed haploid (n) The haploid (n) number for humans is 23 Two representatives of each chromosome type Makes a total of 2n = 46 in each nucleus One set of 23 from individual’s father (paternal) Other set of 23 from individual’s mother (maternal)

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle At the end of S phase: Each chromosome internally duplicated Consists of two identical DNA chains Sister chromatids (two strands of genetically identical chromosomes) Attached together at a single point (called centromere) During mitosis: Centromeres holding sister chromatids together separate Sister chromatids separate Each becomes a daughter chromosome Sisters of each type are distributed to opposite daughter nuclei

Duplicated Chromosomes Biology, 9th ed,Sylvia Mader Chapter 09 Duplicated Chromosomes The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. sister chromatids centromere kinetochore one chromatid a. 9,850 b. © Andrew Syred/Photo Researchers, Inc.

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Just outside the nucleus is the centrosome This is the microtubule organizing center in animal cells Organizes the mitotic spindle Contains many fibers Each fiber is composed of a bundle of microtubules In animals, the centrosome contains two barrel-shaped centrioles Oriented at right angles to each other within the centrosome Each has 9 triplets of microtubules arranged in a cylinder Centrosome was also replicated in S-phase, so there are two centrosomes before mitosis begins

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Phases of Mitosis: Prophase Chromatin has condensed Chromosomes are distinguishable with microscope Each chromosome has two sister chromatids attached at the centromere Nucleolus disappears Nuclear envelope disintegrates Spindle begins to assemble The two centrosomes move away from each other Microtubules form star-like arrays termed asters

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Phases of Mitosis Prometaphase The centromere of each chromosome develops two kinetochores Specialized protein complex One attached to each sister chromatid Physically connect sister chromatids with specialized microtubules (kinetochores) These connect sister chromatids to opposite poles of the mother cell

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Stages of Mitosis Metaphase Chromosomes are pulled around by kinetochore fibers Forced to align across the equatorial plane of the cell Metaphase plate - Represents plane through which mother cell will be divided Anaphase Centromere dissolves, releasing sister chromatids Sister chromatids separate Now called daughter chromosomes Pulled to opposite poles along kinetochore fibers

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Stages of Mitosis Telophase Spindle disappears Now two clusters of daughter chromosomes Still two of each type with all types represented Clusters are incipient daughter nuclei Nuclear envelopes form around the two incipient daughter nuclei Each daughter nucleus receives one chromosome of each type

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Cytokinesis = division of cytoplasm Allocates the mother cell’s cytoplasm equally to daughter nucleus Encloses each daughter cell in its own plasma membrane Often begins in anaphase Animal cytokinesis: A cleavage furrow appears between daughter nuclei Formed by a contractile ring of actin filaments Like pulling on a drawstring Eventually pinches the mother cell in two

Mitosis and Cytokinesis Biology, 9th ed,Sylvia Mader Chapter 09 Mitosis and Cytokinesis The Cell Cycle Cytokinesis in plant cells begins with the formation of a cell plate Rigid cell walls outside plasma membrane do not permit furrowing Many small membrane-bounded vesicles Eventually fuse into one thin vesicle extending across the mother cell The membranes of the cell plate become the plasma membrane between the daughter cells The space between the daughter cells becomes filled with the middle lamella Daughter cells later secrete primary cell walls on opposite sides of the middle lamella

Cytokinesis in Animal Cells Biology, 9th ed,Sylvia Mader Chapter 09 Cytokinesis in Animal Cells The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. X 4,000 Cleavage furrow Contractile ring X 4,000 (top): © Thomas Deerinck/Visuals Unlimited; (bottom): © SPL/Getty RF

Cytokinesis in Plant Cells Biology, 9th ed,Sylvia Mader Chapter 09 Cytokinesis in Plant Cells The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. daughter cells cell plate formation daughter nucleus vesicles containing membrane components fusing to form cell plate nucleoli daughter nucleus (left): © B.A. Palevitz and E.H. Newcomb/BPS/Tom Stack & Associates

Phases of Mitosis in Animal and Plant Cells Biology, 9th ed,Sylvia Mader Chapter 09 Phases of Mitosis in Animal and Plant Cells The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. has centrioles centrosome Animal Cell at Interphase aster 20 µm duplicated chromosome 20 µm spindle pole 9 µm metaphase plate chromosomes at 20µm daughter chromosome 20µm cleavage furrow 16µm nuclear envelope fragments centromere kinetochore nucleolus MITOSIS chromatin condenses nucleolus disappears spindle fibers forming spindle fiber kinetochore kinetochore spindle fiber polar spindle fiber Metaphase Centromeres of duplicated chromosomes of fully formed spindle). Kinetochore spindle are aligned at the metaphase plate (center fibers attached to the sister chromatids come from opposite spindle poles. Telophase Daughter cells are forming as nuclear envelopes and nucleoli reappear. Chromosomes will become indistinct chromatin. Early Prophase Centrosomes have duplicated. Chromatin is condensing into chromosomes, and the nuclear envelope is fragmenting. Prophase duplicated chromosomes are visible. Nucleolus has disappeared, and Centrosomes begin moving apart, and spindle is in process of forming. Prophase duplicated chromosomes are visible. Nucleolus has disappeared, and Centrosomes begin moving apart, and spindle is in process of forming. Anaphase Sister chromatids part and become daughter chromosomes that move toward the spindle poles. In this way, each pole receives the same number and kinds of chromosomes as the parent cell. centrosome lacks centrioles Plant Cell at Interphase 25µm cell wall chromosomes 6.2µm spindle pole lacks centrioles and aster 20µm spindle fibers 6.2µm 6.2µm cell plate 6.6µm Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M. Bostrack/Visuals Unlimited; 28

Phases of Mitosis in Animal and Plant Cells Biology, 9th ed,Sylvia Mader Chapter 09 Phases of Mitosis in Animal and Plant Cells The Cell Cycle Functions of mitosis: Permits growth and repair. In flowering plants, meristematic tissue retains the ability to divide throughout the life of the plant In mammals, mitosis is necessary when: A fertilized egg becomes an embryo An embryo becomes a fetus A cut heals or a broken bone mends

Phases of Mitosis in Animal and Plant Cells Biology, 9th ed,Sylvia Mader Chapter 09 Phases of Mitosis in Animal and Plant Cells The Cell Cycle Stem Cells Many mammalian organs contain stem cells Retain the ability to divide Red bone marrow stem cells divide to produce various types of blood cells Therapeutic cloning to produce human tissues can begin with either adult stem cells or embryonic stem cells Embryonic stem cells can be used for reproductive cloning, the production of a new individual

Reproductive and Therapeutic Cloning Biology, 9th ed,Sylvia Mader Chapter 09 Reproductive and Therapeutic Cloning The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. remove and discard egg nucleus egg remove Go nucleus Implant embryo into surrogate mother fuse egg with Go nucleus Go cells from animal to be cloned culture embryonic stem cells a. Reproductive cloning Clone is born remove and discard egg nucleus egg nervous remove Go nucleus fuse egg with Go nucleus blood Go somatic cells culture embryonic stem cells muscle b. Therapeutic cloning

Which sequence of stages in mitosis is correct? Prophase, anaphase, prometaphase, metaphase, telophase Prophase, telophase, anaphase, prometaphase, metaphase Prophase, prometaphase, metaphase, anaphase, telophase Telophase, anaphase, prophase, prometaphase, metaphase

During cell division, plant cells differ from animal cells by Lacking kinetochores Using actin microtubules for cytokinesis Using cell furrows Forming a cell plate

Not all animals must be diploid in order to be viable organisms Generally, animals build an organisms using the diploid number of chromosomes. However, insects in the order of ants, wasps and bees can use a haploid-diploid system where adults of one sex are formed with a haploid number of chromosomes. This would mean that A single set of chromosomes is sufficient to code for a functional individual A female could determine the sex of the offspring by fertilizing or not fertilizing an egg Not all animals must be diploid in order to be viable organisms All of the above are true

9.3 The Cell Cycle and Cancer Biology, 9th ed,Sylvia Mader Chapter 09 9.3 The Cell Cycle and Cancer The Cell Cycle Abnormal growth of cells is called a tumor Benign tumors are not cancerous Encapsulated Do not invade neighboring tissue or spread Malignant tumors are cancerous Not encapsulated Readily invade neighboring tissues May also detach and lodge in distant places (metastasis) Results from mutation of genes regulating the cell cycle Development of cancer Tends to be gradual May take years before a cell is obviously cancerous

The Cell Cycle and Cancer Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle and Cancer The Cell Cycle Characteristics of Cancer Cells Lack differentiation Are non-specialized Are immortal (can enter cell cycle repeatedly) Have abnormal nuclei May be enlarged May have abnormal number of chromosomes Often have extra copies of genes Do not undergo apoptosis Normally, cells with damaged DNA undergo apoptosis The immune system can also recognize abnormal cells and trigger apoptosis Cancer cells are abnormal but fail to undergo apoptosis

The Cell Cycle and Cancer Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle and Cancer The Cell Cycle Characteristics of Cancer Cells Form tumors Mitosis is normally controlled by contact with neighboring cells – contact inhibition Cancer cells have lost contact inhibition Undergo metastasis Original tumor easily fragments New tumors appear in other organs Undergo angiogenesis Formation of new blood vessels Brings nutrients and oxygen to the tumor

Biology, 9th ed,Sylvia Mader Chapter 09 Progression of Cancer The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. New mutations arise, and one cell (brown) has the ability to start a tumor. primary tumor lymphatic vessel blood vessel Cancer in situ. The tumor is at its place of origin. One cell (purple) mutates further. lymphatic vessel blood vessel Cancer cells now have the ability to invade lymphatic and blood vessels and travel throughout the body. New metastatic tumors are found some distance from the primary tumor.

Cancer Cells vs. Normal Cells Biology, 9th ed,Sylvia Mader Chapter 09 Cancer Cells vs. Normal Cells The Cell Cycle

The Cell Cycle and Cancer Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle and Cancer The Cell Cycle Origin of Cancer Oncogenes Proto-oncogenes promote the cell cycle in various ways If a proto-oncogene is mutated, it may become an oncogene Tumor suppressor genes inhibit the cell cycle in various ways If a tumor suppressor gene becomes inactive, it may promote cancer development Both proto-oncogenes and tumor suppressor genes are normally regulated in coordination with organism’s growth plan

The Cell Cycle and Cancer Biology, 9th ed,Sylvia Mader Chapter 09 The Cell Cycle and Cancer The Cell Cycle Origin of Cancer Chromosomes normally have special material at each end called telomeres These get shorter each cell division When they get very short, the cell will no longer divide Telomerase is an enzyme that maintains the length of telomeres Mutations in telomerase gene: Cause telomeres to continue to lengthen, which Allows cancer cells to continually divide

Biology, 9th ed,Sylvia Mader Chapter 09 Causes of Cancer The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Heredity Radiation sources growth factor growth factor Activates signaling proteins in a stimulatory pathway that extends to the nucleus. Viruses receptor protein Pesticides and herbicides oncogene P a. Influences that cause mutated proto-oncogenes (called oncogenes) and mutated tumor suppressor genes P activated protein signaling P protein signaling Stimulatory pathway phosphate gene product promotes cell cycle b. Effect of growth factor Inhibitory pathway gene product inhibits cell cycle proto-oncogene Codes for a growth factor, a receptor protein, or a signaling protein in a stimulatory pathway. If a proto-oncogene becomes an oncogene, the end result can be active cell division. c. Stimulatory pathway and inhibitory pathway tumor suppressor gene Codes for a signaling protein in an inhibitory pathway. If a tumor suppressor gene mutates, the end result can be active cell division. d. Cancerous skin cell 1,100X d: © Biophoto Associates/Photo Researchers, Inc.

Spreading of cancer by angiogenesis Although cancer may originate in many regions of the body, many patients die from cancerous growths in the lungs, lymph nodes, or liver. These organs are “downstream” of the original site. This is most readily explained as Spreading of cancer by angiogenesis Metastasis occurring more commonly in organs that have a filter effect Proteinase enzymes make cancer particularly damaging to these tissues The results of these organs simply being more susceptible to cancer

9.4 Prokaryotic Cell Division Biology, 9th ed,Sylvia Mader Chapter 09 9.4 Prokaryotic Cell Division The Cell Cycle The prokaryotic chromosome is a ring of DNA Folded up in an area called the nucleoid 1,000 X the length of cell Replicated into two rings prior to cell division Replicated rings attach to the plasma membrane Binary fission Splitting in two Two replicate chromosomes are distributed to two daughter cells Produces two daughter cells identical to original cell – asexual reproduction

Binary Fission The Cell Cycle Biology, 9th ed,Sylvia Mader Chapter 09 Slide #45 Binary Fission The Cell Cycle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. chromosome 1. Attachment of chromosome to a special plasma membrane site indicates that this bacterium is about to divide. cell wall plasma membrane cytoplasm 2. The cell is preparing for binary fission by enlarging its cell wall, plasma membrane, and overall volume. 3. DNA replication has produced two identical chromosomes. Cell wall and plasma membrane begin to grow inward. 4. As the cell elongates, the chromosomes are pulled apart. Cytoplasm is being distributed evenly. 5. New cell wall and plasma membrane has divided the daughter cells. © Dennis Kunkel Microscopy, Inc./Visuals Unlimited SEM 2,345X 45

Functions of Cell Division Biology, 9th ed,Sylvia Mader Chapter 09 Functions of Cell Division The Cell Cycle

Which of the following statements is true about bacterial chromosomes? There is generally only one chromosome in each bacterial cell A bacterial chromosome is wrapped tightly about multiple types of proteins A bacterial chromosome is attached to the nuclear membrane A bacterial chromosome is 100 times the length of the cell