BB1725 Lecture 10 Cell Cycle (4) PDF

BB1725 Biology of the Cell Lecture 10 The Cell Cycle Dr Joseph Hetmanski joseph.hetmanski @brunel.ac.uk Today’s Lecture The lecture today will cover: Cell growth and proliferation The cell cycle By the end of this lecture you should be able to explain: Cell growth and prolife...

BB1725 Biology of the Cell Lecture 10 The Cell Cycle Dr Joseph Hetmanski joseph.hetmanski @brunel.ac.uk Today’s Lecture The lecture today will cover: Cell growth and proliferation The cell cycle By the end of this lecture you should be able to explain: Cell growth and proliferation The stages of the cell cycle The role of some key proteins in the cell cycle Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 2 Cell Growth and Proliferation Cell Growth – increase in cell size (Hypertrophy) Proliferation - increase in cell number (Hyperplasia) by cell division occurring faster than Figure 17–1 The cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 cell death W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 3 Multicellular organisms Normal rate of cell division: Frog embryo cells - 30 mins Gut lining (epithelial cells) - 12 hours Skin fibroblasts in culture - 24 hours Human liver cells - 1 Figure 17–1 The cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 year W.W. Norton & Company, Inc. Neurons – never! (although Brunel they University London - BB1720 - Cellare Biology - Week 7 - Lecture 14 - 2023/24 4 Cell cycle events Generation of 2 daughter cells from a mother cell Cell Division - Mitosis – a short time in the cell’s life Interphase - The rest Figure 17–1 The cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 of the time! W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 5 Major Events of the cell cycle Two major events in the cell cycle 1.S-phase (synthesis phase) Chromosomes duplicate 2.M-phase (mitotic phase) Duplicated chromosomes segregate into daughter cells Figure 17–2 The major events of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 6 Phases of the Cell Cycle There are four phases: The S-phase (chromosomal duplication) and the M- phase (separation) Two Gap phases, G1 and G2, which separate the S and M phases Gap phases allow time for growth and duplication of proteins Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 7 Phases of the Cell Cycle Order of the phases 1.G1 phase 2.S phase - DNA 3.G2 phase 4.M phase - Division G1, S and G2 combined are called the Interphase Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 8 Phases of the Cell Cycle Figure 17–3 The events of eukaryotic cell division as seen under a microscope Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. G1 phase - Interphase Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 9 Phases of the Cell Cycle Figure 17–3 The events of eukaryotic cell division as seen under a microscope Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. S phase - DNA replication - Interphase Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 10 Phases of the Cell Cycle Figure 17–3 The events of eukaryotic cell division as seen under a microscope Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. G2 phase - Interphase Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 11 Phases of the Cell Cycle Figure 17–3 The events of eukaryotic cell division as seen under a microscope Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. M phase - Division Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 12 M phase - Division - Mitosis Stages of Mitosis (cell division) can be seen under the microscope More on the stages in the next lecture… https://micro.magnet.fsu.edu/cells/fluorescencemitosis/ index.html Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 13 Interphase - The rest of the time Growth Performing normal cellular functions Duplication of: Protein content RNA content Chromatin (DNA and protein) Organelles – e.g. Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Mitochondria Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 14 Interphase - Protein Concentration 1 Protein levels will halve as the cell divides As the cell prepares for division, protein levels will 0.5 increase M Interphase M Cell Cycle Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 15 Interphase - RNA Concentration 1 RNA levels will halve as the cell divides As the cell prepares for division, RNA levels will 0.5 increase M Interphase M Cell Cycle Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 16 Interphase - Organelles 1 Organelles will halve as the cell divides As the cell prepares for division, organelles will 0.5 increase M Interphase M Cell Cycle Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 17 Interphase - DNA S Phase DNA levels will 2 halve as the cell divides As the cell prepares for division, DNA levels will double, until cell division 1 M Interphase M occurs Cell Cycle Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 18 DNA synthesis The genome is duplicated during a discrete phase of the cell cycle DNA synthesis phase: S-phase DNA replication Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. occurs Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 19 Between M and S Early embryos S-phase quickly follows M- phase Usually there is a delay between M and S And another between S and M Gaps Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Growth periods Norton & Company, Inc. G1 phase and G2 phase Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 20 Regulated cell cycles Early embryos Cell cycle is free running Cells need to replicate for development Somatic cells Cell cycle regulated Figure 17–4 The four phases of the cell cycle Cell cycle controlled Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 21 Why the difference? Early embryos - rapid generation of new cells Individual cells get smaller See the frog video yesterday Somatic cells - need to double in size each generation Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. New cells generated Norton & Company, Inc. Organism gets bigger Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 22 Multicellularity Becoming multicellular requires cooperation Increase in cell number only: When growing (embryo) When replacing worn- out tissue (skin, gut Figure 17–4 The four phases of the cell cycle lining, blood cells) Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. When repairing wounds Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 23 Control of the cell cycle How is the cell cycle controlled? The arm represents the process and rotates clockwise, trigger the processes (yellow boxes) Figure 17–8 The control of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 24 Signals Most cells do not divide constantly Most cell are in a resting state G0 This is called - Quiescence Also called the G0 phase G0 can be viewed as ‘holding’ in G1 Figure 17–4 The four phases of the cell cycle Requires stimulation to Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. move out of G0 to G1 Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 25 Stimulation Most cells require a stimulus to enter the cell division cycle: Growth factors G0 Produced by other cells “Sensed” at cell surface Bind to receptors Signal transduction to the nucleus Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Stimulate cell division (activation of genes) Stimulus Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 26 Molecular Mechanisms What is the nature of the molecules G0 controlling the cell cycle? How do they operate? Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Stimulus Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 27 Fusion experiments Used cultured cells to explore the control mechanisms Joined a cell in mitosis with a cell in interphase Result: Induced condensation of chromosomes Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 28 M-phase dominance Dominant! Regardless of the phase of the recipient cell (G1, S or G2) M is always dominant Injection of cytoplasm from M Figure 17–4 The four phases of the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. phase cell is enough Norton & Company, Inc. to drive the process Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 29 MPF Because the activity could cause mitosis it was termed Mitosis-promoting factor (maturation-promoting factor; MPF) Now biochemically defined as a complex of proteins containing a catalytic subunit and Figure 17–9 Two key components of the cell- cycle control system regulatory subunit Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 30 Nobel 2001 The Nobel Prize in Physiology or Medicine 2001 was awarded jointly to Leland H. Hartwell, Tim Hunt and Sir Paul M. Nurse "for their discoveries of key regulators of the cell cycle." Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 31 Catalytic subunit CDK (also called CDC2) [Cyclin dependent kinase] Master regulator of the cell cycle Kinase enzyme Adds phosphate groups to amino acids in polypeptides Requires association with a regulatory subunit for activity https://www.ptglab.com/products/featured- CDK1, CDK2, CDK4/6 have products/cell-cycle-and-checkpoint-controls/ different roles Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 32 Regulatory subunit Cyclins Undergoes cycles of synthesis and degradation So-called because they undergo rounds of synthesis and degradation during the cell cycle* Figure 17–9 Two key components of the cell- cycle control system There are four classes… Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. *Actually because the discoverer Tim Hunt was passionate about cycling Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 33 Cyclins Four classes: 1.G1/S-cyclin [cyclin E] - activates Cdk late in G1 2.S-cyclin [cyclin A] - binds Cdk at start, helps drive chromosome division 3.M-cyclin [cyclin B] - activates Cdk - G2-M transition Figure 17–9 Two key components of the cell- cycle control system Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. 4.G1-cyclin [cyclin D] - controls Brunel University LondonG 1/S-cyclin - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 34 Cyclin alternative names Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 Cyclin-Cdk complexes in the cell cycle Figure 17–10 Cyclin–Cdk complexes of the cell-cycle control system Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. G1/S-cyclin [cyclin E] - activates Cdk late in G1 (Cdk levels are constant) Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 36 Cyclin-Cdk complexes in the cell cycle Figure 17–10 Cyclin–Cdk complexes of the cell-cycle control system Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. S-cyclin [cyclin A] - binds Cdk at start, helps drive chromosome division (Cdk levels are constant) Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 37 Cyclin-Cdk complexes in the cell cycle Figure 17–10 Cyclin–Cdk complexes of the cell-cycle control system Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. M-cyclin [cyclin B] - activates Cdk - G2-M transition (Cdk levels are constant) Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 38 How do Cyclin-Cdk complexes work? Cyclin does not just activate Cdk but also helps position the kinase (Cdk) next to the proteins that require phosphorylation to drive the next step Figure 17–9 Two key components of the cell- cycle control system Molecular Biology of the Cell - Seventh Edition - of the cycle Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 39 Overview Figure 17–20 Sequential activation of Cdks during the cell cycle Molecular Biology of the Cell - Seventh Edition - Copyright © 2022 W.W. Norton & Company, Inc. Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 40 Cell cycle phase imaging Imaging probes such as FUCCI (Fluorescent ubiquitination-based cell cycle indicator) can indicate cell cycle stage by colour changes https://www.mblbio.com/bio/g/product/flprotein/fucci.html Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 What happened next? 1 We have been suppressing CDK1 activity with an inhibitor and then remove the inhibitor Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 What happened next? 2 The cells are depleted of both cyclin A and cyclin B Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 Summary There are two major events in the cell cycle S-phase - chromosome duplication M-phase - segregation of duplicated chromosomes The S and M phases are separated by gap (G1 and G2) phases - G1 - S - G2 - M Cells are held on a G0 phase (part of G1) The cell cycle is controlled by Cdk and four cyclins Cell cycle can be controlled via these Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 44 Next Week Mitosis Meiosis Cell membranes Membrane transport Introduction to organelles Cytoskeleton Cell migration Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 45 Suggested Reading Explore the material for this week on Brightspace Molecular biology of the cell by Alberts et al 7th Ed. - Chapter 14 Brunel University London - BB1720 - Cell Biology - Week 7 - Lecture 14 - 2023/24 46 Questions?