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The Cell Cycle and Cell Division. 11 The Cell Cycle and Cell Division. 11.1 How Do Prokaryotic and Eukaryotic Cells Divide? 11.2 How Is Eukaryotic Cell Division Controlled? 11.3 What Happens During Mitosis? 11.4 What Role Does Cell Division Play in a Sexual Life Cycle?.
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11 The Cell Cycle and Cell Division • 11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • 11.2 How Is Eukaryotic Cell Division Controlled? • 11.3 What Happens During Mitosis? • 11.4 What Role Does Cell Division Play in a Sexual Life Cycle?
11 The Cell Cycle and Cell Division • 11.5 What Happens during Meiosis? • 11.6 In a Living Organism, How Do Cells Die? • 11.7 How Does Unregulated Cell Division Lead to Cancer?
11 The Cell Cycle and Cell Division The first human cells to be grown in the laboratory came from a woman with cervical cancer in 1957. The cells grew so well and are so robust, they have been used in research to this day. Opening Question: What makes HeLa cells reproduce so well in the laboratory?
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • The life cycle of an organism is closely linked to cell division. • Cell division is important in growth and repair of tissues in multicellular organisms, and in the reproduction of all organisms.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Four events must occur for cell division: • A reproductive signal initiates cell division • Replication of DNA • Segregation: distribution of DNA into two new cells • Cytokinesis: separation of cellular material into the two new cells
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • In prokaryotes, binary fission results in two new single-celled organisms. • External factors such as nutrient concentration and environmental conditions are the reproductive signals. • For many bacteria, abundant food supplies speed up the division cycle.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Most prokaryotes have one chromosome, a single molecule of DNA. Often forms a circle, but is compacted and folded. • Two important regions: • ori—where replication starts (origin) • ter—where replication ends (terminus)
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Replication occurs as the DNA is threaded through a “replication complex” of proteins. • The ori regions move toward opposite ends of the cell, aided by special proteins.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • When replication is complete, the daughter DNA molecules are segregated at opposite ends. • In rapidly dividing prokaryotes, DNA replication occupies the entire time between cell divisions.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Cytokinesis begins by a pinching in of the plasma membrane; protein fibers form a ring. • New cell wall materials are synthesized, resulting in separation of the two cells.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • In eukaryotes, signals for cell division are related to the needs of the entire organism. • Many cells in multicellular organisms become specialized and seldom divide. • Eukaryotes usually have many chromosomes; replication and segregation are more intricate.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Newly replicated chromosomes are closely associated (sister chromatids). • Mitosis separates them into two new nuclei. • Cytokinesis proceeds differently in animal and plant cells (plants have cell walls).
11.1 How Do Prokaryotic and Eukaryotic Cells Divide? • Cells resulting from mitosis are genetically identical to the parent cell. • Meiosis is nuclear division in cells involved in sexual reproduction. • The cells resulting from meiosis are not identical to the parent cells. It results in new gene combinations.
11.2 How Is Eukaryotic Cell Division Controlled? • Cell cycle: period from one cell division to the next; divided into mitosis/cytokinesis and interphase. • Interphase: nucleus is visible and cell functions, including DNA replication, occur; begins after cytokinesis, ends when mitosis starts (M phase). • Duration of interphase is highly variable.
11.2 How Is Eukaryotic Cell Division Controlled? • Interphase has three subphases: G1, S, and G2 • G1: between cytokinesis and S phase; chromosomes are single, unreplicated structures.Duration of G1 is variable, from a few minutes to years. Some cells enter a resting phase (G0).
11.2 How Is Eukaryotic Cell Division Controlled? • At the G1-to-S transition the commitment is made to DNA replication and subsequent cell division. Now called the restriction (R) point. • S phase: DNA replicates; sister chromatids remain together. • G2:cell prepares for mitosis (e.g., by synthesizing structures to move the chromatids).
11.2 How Is Eukaryotic Cell Division Controlled? • Specific signals trigger the transition from one phase to another. • Identification of these signals came from cell fusion experiments. • For example, cells in the S phase produce a substance that activates DNA replication.
Working with Data 11.1: Regulation of the Cell Cycle • To study regulation of the cell cycle, HeLa cells were fused using the membrane-enclosed Sendai virus of mice. • DNA of cells in the S phase was labeled with radioactive thymidine. • Cells in S and G1 were then fused and again exposed to radioactive thymidine.
Working with Data 11.1: Regulation of the Cell Cycle • After fusion, the percent of G1 nuclei that had incorporated new label (had replicated their DNA) was calculated:
Working with Data 11.1: Regulation of the Cell Cycle • S and G2 cells were then fused in various combinations and the percent of cells in mitosis determined:
Working with Data 11.1: Regulation of the Cell Cycle • Question 1: • According to Figure A, how long did it take for all the G1 nuclei in the G1/S cells to become labeled?
Working with Data 11.1: Regulation of the Cell Cycle • Question 2: • Examine the data for fused G1/G1 cells and unfused G1 cells in Figure A. • Explain why these were appropriate controls for the experiments. • When did these nuclei become labeled? • Compare these times with each other and with the G1/S nuclei and discuss.
Working with Data 11.1: Regulation of the Cell Cycle • Question 3: • Examine the data in Figure B. • Why did it take longer for the cells in S phase to begin mitosis than it did for the cells in G2?
Working with Data 11.1: Regulation of the Cell Cycle • Question 4: • According to Figure B, did fusion with G2 cells alter the timing of mitosis in the S cell nuclei? • Explain what this means in terms of control of the cell cycle.
11.2 How Is Eukaryotic Cell Division Controlled? • The signals act through cyclin-dependent kinases (Cdk’s). • Protein kinases catalyze transfer of a phosphate group from ATP to a protein (phosphorylation). The shape and function of the protein changes. • Cdk’s play important roles in the cell cycle.
11.2 How Is Eukaryotic Cell Division Controlled? • Cdk is activated by binding to cyclin (allosteric regulation); this alters its shape and exposes the active site. • There are many different cyclin–cdk complexes acting at different stages of the cell cycle.
Figure 11.6 Cyclin-Dependent Kinases Regulate Progress through the Cell Cycle
11.2 How Is Eukaryotic Cell Division Controlled? • At the G1-S transition: • Progress past the restriction point depends on retinoblastoma protein(RB). • RB normally inhibits the cell cycle, but when phosphorylated by G1-S cyclin-Cdk, RB becomes inactive and no longer blocks the cell cycle.
11.2 How Is Eukaryotic Cell Division Controlled? • Progress through the cell cycle depends on Cdk activity, so regulating Cdk is a key to regulating cell division. • Cdk’s can be regulated by the presence or absence of cyclins.
11.2 How Is Eukaryotic Cell Division Controlled? • Cyclin–Cdk’s act at cell cycle checkpoints to regulate progress. • Example: At checkpoint R, if DNA is damaged, p21 protein is made. p21 binds to G1 Cdk’s, preventing their activation. The cell cycle stops while DNA is repaired.
11.2 How Is Eukaryotic Cell Division Controlled? • The cell cycle is also influenced by external signals. • Some cells divide infrequently or go into G0. They must be stimulated by growth factors to divide. • Platelet-derived growth factor: from platelets that initiate blood clotting; stimulates skin cells to divide and heal wounds.
11.2 How Is Eukaryotic Cell Division Controlled? • Interleukins and erythropoietin are growth factors that stimulate division and specialization of blood cells. • Growth factors bind to specific receptors on target cells and activate signal transduction pathways that end with cyclin synthesis, thereby activating Cdk’s and the cell cycle.
11.3 What Happens during Mitosis? • DNA molecules are complexed with proteins to form chromatin. • After replication, the sister chromatids are held together during G2 by proteins called cohesins. • At mitosis the cohesin is removed, except at the centromere region. Other proteins called condensins coat the DNA molecules and make them more compact.
11.3 What Happens during Mitosis? • Eukaryotic DNA molecules are extensively “packed” and organized by histones—proteins with positive charges that attract the negative phosphate groups of DNA. • Interactions result in the formation of beadlike units, or nucleosomes.
Figure 11.9 DNA is Packed into a Mitotic Chromosome (Part 1)
Figure 11.9 DNA is Packed into a Mitotic Chromosome (Part 2)
11.3 What Happens during Mitosis? • During interphase, the DNA is less densely packed and is accessible to proteins involved in replication. • Once the mitotic chromosome has formed, it is inaccessible to replication and transcription factors.
11.3 What Happens during Mitosis? • Mitosis (M phase) ensures accurate segregation of chromosomes to daughter cells. • The phases of mitosis: • Prophase: chromatin condenses and chromatids become visible • Prometaphase: nuclear envelope breaks down and chromosomes attach to the spindle
11.3 What Happens during Mitosis? • Metaphase: chromosomes line up at the midline • Anaphase: chromosomes separate and move to opposite poles • Telophase: nuclear envelopes reform, spindle disappears, chromosomes become less compact
