Two from One - A Short Introduction to Cell Division Mechanisms

PREFACE 5 INTRODUCTION 6 CHAPTER 1 - HISTORY AND CONTEXT 8 From cells to their nuclei 8 The cell theory 9 Mitosis 10 The chromosome theory of heredity 12 DNA 15 Cell cycles come in many flavors 17 CHAPTER 2 - CELL GROWTH AND DIVISION 21 Balanced growth and cell proliferation 21 Measures of cell growth 24 The relationship between cell growth and division 27 Patterns of growth in the cell cycle 29 Amoeba cell growth 30 Fission yeast growth 30 Budding yeast growth 31 Mammalian cell growth 33 Sizers, Adders, Timers 33 CHAPTER 3 - ASSAYING CELL CYCLE PROGRESSION 40 Measuring cell cycle phases 40 Single-cell imaging 40 Labelled mitoses 41 Frequency distributions 43 Growth limitations and variations in the duration of cell cycle phases 46 Synchronous cultures 48 How can one induce synchrony? 48 Selecting for synchrony 51 Elutriation: The mother of all synchrony selections 52 CHAPTER 4 - THE MASTER SWITCH 55 Genetic analyses leading the way 55 The cdc28 mutant of budding yeast 55 From the wee1 to the cdc2 mutant of fission yeast 59 What is true for one is true for all 61 Author: M. Polymenis Book title: Two from One Page - 9 All roads lead to the same control system 61 Cyclins 62 MPF 64 Making sense of it all 68 Cyclins galore in budding yeast 68 G1 cyclins 69 Back to wee1 70 CHAPTER 5 - CONTROLLING THE MASTER SWITCH 73 Cyclins in Cdk complexes 74 Cdk as a target of phosphorylations 76 Activating phosphorylation 76 Inhibitory phosphorylation 77 Other proteins in cyclin/Cdk complexes 77 Cdk inhibitors 78 Cip/Kip proteins 79 INK4 proteins 80 Cks1 80 What are its targets and how Cdk phosphorylates them 80 Defining the Cdk substrate universe 80 Cyclin the recruiter 82 Here comes Cks1 83 Ordering Cdk phosphorylation in the cell cycle 85 Order from intrinsic Cdk activity 85 Order and precision from specificity 87 CHAPTER 6 - A FULL CIRCLE OF THE SWITCH 90 Modeling a cell cycle oscillator 90 The M-Cdk switch 93 Exit from interphase into mitosis 93 The anaphase promoting complex (APC) 94 From metaphase to anaphase 94 Flipping the M-Cdk switch off 95 Unsolved problem: 'Sizing' the M-Cdk switch 98 The G1/S Cdk switch 98 G1-Cdk activates G1/S transcription 99 Doing away with transcriptional inhibitors 99 The G1 cyclin Cln3 rises and targets Whi5 100 Whi5 is diluted away as cells grow in size 102 Positive feedback at the G1/S switch 102 Negative feedback at the G1/S switch 103 Physiological relevance of G1/S switch in cancer 104 Transcriptional waves until the end of the cell cycle 105 Comments on overall gene expression in the cell cycle 107 CHAPTER 7 - DUPLICATING THE GENOME 109 DNA replication 109 Setting the stage 110 Origin firing 113 Chromatin 115 Sisters stay together 116 Checkpoints 119 The general concept 119 DNA damage checkpoint 120 CHAPTER 8 - SEGREGATING THE CHROMOSOMES 124 Blind men's riddle 124 The mitotic spindle 125 Tubulin 126 MTs are dynamic 127 Scaling the spindle 130 The microtubule organizing centers (MTOCs) 131 The kinetochore 135 Kinetochore-MT interactions: May the force be with you 136 The spindle assembly checkpoint (SAC) 140 CHAPTER 9 - SEGREGATING ORGANELLES AND THE CYTOPLASM 143 The Golgi 145 Mitochondria 147 Lysosomes and vacuoles 150 Mitotic fragmentation of the nuclear envelope 151 Cytokinesis: Two from One 152 Position 153 Assemble 156 Contract 158 LIST OF PROTEINS OR COMPLEXES AND THEIR FUNCTION 160 REFERENCES