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