Chapter 9 The Cell Cycle Overview: The Key Roles of Cell Division Key Concepts • The continuity of life is based on the reproduction of cells, or cell division 9.1 Most cell division results in genetically identical cells 9.2 The mitotic phase alternates with interphase in the cell cycle 9.3 The eukaryotic cell cycle is regulated by a molecular control system How do dividing cells distribute chromosomes to daughter cells? © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. The functions of cell division 100 m (a) Reproduction 50 m (b) Growth and development 20 m © 2016 P Ed ti Life span of a cell • • • • • Skin cells: 1-34 days Stomach lining cells: 2 days Red blood cells: 120 days Bone cells: 25-30 years Nerve cells & Heart cells cannot be replaced (c) Tissue renewal I Multicellular organisms depend on cell division for: - Development from a fertilized cell - Growth and development - Repair of damaged tissue - Replacing old cells Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division © 2016 Pearson Education, Inc. 1 Concept 9.1: Most 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 • Most cell division results in daughter cells with identical genetic information, DNA • The exception is meiosis, a special type of division that can produce sperm and egg cells Eukaryotic Chromatin & Chromosomes - Genetic material in eukaryotes is packaged in the nucleus into discrete chromosomes - Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus - Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein • Condensed & Visible when cell division is occurring • Otherwise, called chromatin, the uncondensed form © 2016 Pearson Education, Inc. Fig. 16-21a Fig. 16-21b Chromatid (700 nm) 30-nm fiber Nucleosome (10 nm in diameter) DNA double helix (2 nm in diameter) Loops Scaffold H1 DNA, the double helix 300-nm fiber Histone tail Histones Histones Nucleosomes, or “beads on a string” (10-nm fiber) Replicated chromosome (1,400 nm) 30-nm fiber Chromosomes in Human cells Looped domains (300-nm fiber) Metaphase chromosome Chromosomes in Human cells In animals Somatic cells (non reproductive cells) have two sets of chromosomes, 46 chromosomes in a human somatic cell - 44 Autosomes + XY in males - 44 Autosomes +XX in females SOMATIC CELL - All Body cells, except gametes - GAMETE reproductive cells; sperm & egg - - 23 chromosomes 46 chromosomes - Diploid: Two sets of 23 (2n) - Haploid: One set of 23 (n) - Produced by mitosis - Produced by meiosis (chapter 10) Gametes (reproductive cells: sperm cells & egg cells) have one set of chromosomes, 23 in a human gamete cell - A Sperm cell in Males has 22 Autosomes +X or 22 Autosomes + Y - An Egg cell in Females has 22 Autosomes + X http://passel.unl.edu/Image/siteImages/SomaticGameteCellLG.gif 2 Figure 12.5-3 Chromosomes A highly condensed, duplicated human chromosome (SEM) 1 The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication Sister chromatids 2 Sister chromatids Centromere 0.5 m Separation of 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 3 © 2016 Pearson Education, Inc. Distribution of Chromosomes During Eukaryotic Cell Division In preparation for cell division - DNA is replicated and the chromatin condense to form chromosomes Each duplicated chromosome Phases of the Cell Cycle The mitotic phase alternates with interphase in the cell cycle 1. Interphase, including cell growth and copying of chromosomes in preparation for cell division 2. Mitotic (M) phase, including mitosis and cytokinesis - Has two sister chromatids, which separate during cell division - The two sister chromatids are held together by centromere Interphase Interphase (about 90% of the cell cycle) can be divided into subphases - G1 phase (“first gap”) - S phase (“synthesis” Each chromosome now consists of 2 chromatids) - G2 phase (“second gap”) The cell grows during all three phases, but chromosomes are duplicated(replicated) only during the S phase. Interphase (about 90% of the cell cycle) can be divided into subphases • G1 phase: synthesis of proteins & organelles • S phase: synthesis of DNA - Each chromosome now consists of 2 chromatids • G2 phase: synthesis of proteins & organelles • G0 phase: cells that do not divide and exit the cell cycle • The cell grows during all three phases, but chromosomes are duplicated only during the S phase © 2016 Pearson Education, Inc. 3 Cell Division Mitosis is conventionally divided into five phases Eukaryotic cell division consists of - Prophase - Mitosis, the division of the nucleus Sometimes grouped together as “Prophase” - Prometaphase - Cytokinesis, the division of the cytoplasm - Metaphase In meiosis - Anaphase - Gamete cells are produced after a reduction in chromosome number Meiosis yields non identical daughter cells that have half as many chromosomes as the parent cell - Telophase Cytokinesis overlaps the last stages of mitosis © 2016 Pearson Education, Inc. MITOSIS INTERPHASE G2 of Interphase Centrosomes (with centriole pairs) Prophase/Prometaphase Prophase Chromosomes (duplicated, uncondensed) Early mitotic Centromere spindle Aster Chromatin condenses to form chromosomes The nucleoli and nuclear envelop disappears Mitotic spindle begin to form. Microtubules extend from centrosomes and attach to Kinetochore (region on the chromosomes near the centromere) The centrosomes move away from each other Nucleolus Nuclear envelope Plasma membrane Two sister chromatids of one chromosome © 2016 Pearson Education, Inc. MITOSIS Prometaphase Fragments of nuclear envelope Metaphase Nonkinetochore microtubules Metaphase plate Metaphase • Metaphase is the longest phase of mitosis. • Chromosomes are fully condensed and most visible at this stage • The sister chromatids are arranged at the metaphase plate, or the equator of the cell, an imaginary plane, equidistant from the spindle’s two poles. Kinetochore Kinetochore microtubules Spindle Centrosome at one spindle pole © 2016 Pearson Education, Inc. 4 Anaphase Telophase • The sister chromatids separate and become full-fledged chromosomes • Each freed chromatid (now referred to as a chromosome or daughter chromosome) is pulled toward the opposite pole of the cell • The two sets of chromosomes have reached the opposite poles of the cell • The chromosomes decondense. • The mitotic spindle disappears • Two daughter nuclei begin to form, one at each pole • The nuclear envelope and nucleolus reappear • Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell • *Mitosis, the division of one nucleus into two genetically identical nuclei, is now complete MITOSIS Anaphase CONCEPT CHECK Telophase and Cytokinesis Cleavage furrow Nucleolus forming WHICH of the following happen during mitosis? A. B. C. D. Daughter chromosomes condensing of the chromosomes synthesis of DNA formation of the spindle uncoupling of the chromatids at the centromeres Nuclear envelope forming © 2016 Pearson Education, Inc. THINK PAIR SHARE In Humans: Before S phase How many chromosomes? How many chromatids? 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, a type of microtubule organizing center After S phase How many chromosomes? How many chromatids? © 2016 Pearson Education, Inc. 5 Aster The mitotic spindle at metaphase Centrosome Sister chromatids Metaphase plate (imaginary) 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 spindle’s two poles Kinetochores Microtubules Chromosomes Overlapping nonkinetochore microtubules Kinetochore microtubules 1 m 0.5 m © 2016 Pearson Education, Inc. Centrosome © 2016 Pearson Education, Inc. Figure 9.9 At which end do kinetochore microtubules shorten during anaphase? Experiment - 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 Results Kinetochore Spindle pole Conclusion Mark - Chromosomes are also “reeled in” by motor proteins at spindle poles, and microtubules depolymerize after they pass by the motor proteins Chromosome movement Kinetochore Motor Microtubule protein Chromosome Tubulin subunits At anaphase, the chromosome movement is correlated with kinetochore microtubules shortening at their kinetochore ends and not at the spindle pole ends. © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Animation: Cytokinesis Nonkinetochore 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 parent cell Cytokinesis begins during anaphase or telophase, and the spindle eventually disassembles © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. 6 Cytokinesis in animal and plant cells Cytokinesis: A Closer Look (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM) In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow In plant cells, a cell plate forms during cytokinesis Cleavage furrow Contractile ring of microfilaments © 2016 Pearson Education, Inc. © 2016 P Mitosis in a plant cell Nucleus Chromosomes Nucleolus condensing Ed ti 100 m Vesicles Wall of forming parent cell Cell cell plate plate Daughter cells 1 m New cell wall Daughter cells I Bacterial cell division by binary fission Chromosomes Origin of replication Chromosome replication begins. E. coli cell Two copies of origin Cell wall Plasma membrane Bacterial chromosome 10 m Prometaphase Cell plate Prophase One copy of the origin is now at each end of the cell. Origin Origin Replication finishes. Metaphase Anaphase Two daughter cells result. Telophase © 2016 Pearson Education, Inc. © 2016 Pearson Education Inc Binary Fission in Bacteria The Evolution of Mitosis Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission - Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission - In E. coli, the single chromosome replicates, beginning at the origin of replication - Certain protists (dinoflagellates, diatoms, and some yeasts) exhibit types of cell division that seem intermediate between binary fission and mitosis - The two daughter chromosomes actively move apart while the cell elongates - The plasma membrane pinches inward, dividing the cell into two © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. 7 Concept Check All of the following happen during mitosis except ______________________ . CONCEPT Check CHECK Concept Which of the following reproduce by binary fission? A. bacteria A. condensing of the chromosomes B. synthesis of DNA C. formation of the spindle D. uncoupling of the chromatids at the centromeres The eukaryotic cell cycle is regulated by a molecular control system B. archaea C. chloroplasts D. mitochondria E. All of these choices are correct. Do molecular signals in the cytoplasm regulate the cell cycle? Experiment Experiment 1 Experiment 2 - The frequency of cell division varies with the type of cell - These differences result from regulation at the molecular level S G1 S S M G1 Results - Cancer cells manage to escape the usual controls on the cell cycle G1 nucleus immediately entered S phase and DNA was synthesized. M M G1 nucleus began mitosis without chromosome duplication. Conclusion: Molecules present in the cytoplasm control the progression to S and M phases. © 2016 Pearson Education, Inc. Evidence for Cytoplasmic Signals - The cell cycle is driven by specific signaling molecules present in the cytoplasm - Some evidence for this hypothesis comes from experiments with cultured mammalian cells - Cells at different phases of the cell cycle were fused to form a single cell with two nuclei at different stages - Cytoplasmic signals from one of the cells could cause the nucleus from the second cell to enter the “wrong” stage of the cell cycle © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. 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 © 2016 Pearson Education, Inc. 8 Mechanical analogy for the cell cycle control system G1 checkpoint For many cells, the G1 checkpoint seems to be the most important Control system G1 M If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide S If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase G2 M checkpoint G2 checkpoint © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. The clock has specific checkpoints • Cell receives a go-ahead signal at G1 it will go through G1, S, G2 and Mitosis and divide • Cells enter G0 phase if it does not receive the go-ahead signal G1 checkpoint G1 G1 M G2 M G0 G2 M checkpoint Anaphase G1 Without go-ahead signal, cell enters G0. G1 With go-ahead signal, cell continues cell cycle. (a) G1 checkpoint Prometaphase G2 checkpoint Metaphase Without full chromosome attachment, stop signal is received. With full chromosome attachment, go-ahead signal is received. (b) M checkpoint © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Scalpels Scalpels The cell cycle is regulated by a set of regulatory proteins and protein complexes including kinases and proteins called cyclins 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 AAsample sampleofof human humanconnective connective tissue tissueisiscut cut up upinto intosmall small pieces. pieces. Petri Petri dish dish Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. Cells are transferred to culture vessels. Without PDGF © 2016 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 PDGF is added to half the vessels. With PDGF Cultured fibroblasts (SEM) 10 m © 2016 Pearson Education, Inc. © Pearson Education, Inc. © 2016 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. 9 Figure 9.18 Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing Anchorage dependence: cells require a surface for division Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide Density-dependent inhibition: cells form a single layer Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Density-dependent inhibition: cells divide to fill a gap and then stop 20 m (a) Normal mammalian cells 20 m (b) Cancer cells © 2016 Pearson Education, Inc. © 2016 Pearson Education, Inc. Loss of Cell Cycle Controls in Cancer Cells A normal cell is converted to a cancerous cell by a process called transformation Cancer cells do not respond to signals that normally regulate the cell cycle Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue Cancer cells do not need growth factors to grow and divide If abnormal cells remain only at the original site, the lump is called a benign tumor - 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 Malignant tumors invade surrounding tissues and undergo metastasis, exporting cancer cells to other parts of the body, where they may form additional tumors How a tumor suppressor gene blocks the cell cycle © 2016 Pearson Education, Inc. 5 m © 2016 Pearson Education, Inc. Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment The growth and metastasis of a malignant breast tumor Breast cancer cell (colorized SEM) Medical treatments for cancer are becoming more “personalized” to an individual patient’s tumor Metastatic tumor Lymph vessel Tumor Blood vessel Cancer cell Glandular tissue A tumor grows from a single cancer cell. © 2016 Pearson Education, Inc. 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. Henrietta Lacks HeLa cancer cells © 2016 Pearson Education, Inc. 10 THINK/PAIR/SHARE Summary of key concepts: mitotic phase and interphase P G1 Cytokinesis Mitosis You get an knee scrape and your skin cells are getting ready to divide and repair the damage. One of these skin cells has gone through G2 phase and is about to enter Mitosis. S G2 MITOTIC (M) PHASE 1. How many chromosomes does it contain? 2. How many chromatids does it contain? Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase © 2016 Pearson Education, Inc. You should now be able to 1. 2. 3. 4. 5. 6. 7. 8. Describe the structure of the prokaryotic genome and the eukaryotic genome List the phases of the cell cycle; describe the sequence of events during each phase List the phases of mitosis and describe the events characteristic of each phase Role of kinetochore microtubules and nonkinetochore microtubules Compare cytokinesis in animals and plants What is binary fission? Difference between normal cells and cancer cells Distinguish between benign, malignant, and metastatic tumors 11