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SC430 Molecular Cell Biology • Welcome to Unit 8 Seminar with Dr Hall-Pogar • Tonight we will discuss – Cell Cycle – I will be available at AIM:KaplanHallPogar before and throughout the seminar if you have any questions or issues. • We will begin promptly at 8:00pmET Unit Review • DB • No Project! 2 Overview: The Key Roles of Cell Division • The ability of organisms to reproduce best distinguishes living things from non-living matter • The continuity of life is based upon the reproduction of cells, or cell division • Cell division is integral part of cell cycle 3 Types of cell division • Prokaryotes – Binary fission • Eukaryotes – Mitosis: • Growth, development & repair • Asexual reproduction (yields genetically identical cells) • Occurs in somatic (body) cells – Meiosis: • Sexual reproduction (yields genetically different cells with half the # of chromosomes) • Occurs in specific reproductive cells • Yields gametes (e.g., eggs & sperm) or spores Cell Cycle The Cell’s Time Clock • Smallest unit of life – all living things must reproduce • Cells replicate for growth, replacement, and repair • Cell division requires Mitosis & Cytokinesis Cytokinesis 5 Phases of the Cell Cycle • The cell cycle consists of – Mitotic (M) phase (mitosis and cytokinesis) – Interphase (cell growth and copying of chromosomes in preparation for cell division) • Interphase (about 90% of the cell cycle) can be divided into subphases: – G1 phase (“first gap”) – S phase (“synthesis”) – G2 phase (“second gap”) 6 INTERPHASE G1 S (DNA synthesis) G2 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 clock • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received • For many cells, the G1 checkpoint seems to be the most important one 8 G1 checkpoint Control system G1 M M checkpoint G2 checkpoint G2 S G0 G1 checkpoint G1 If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle. G1 If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. Cyclins & Cylin-Dependent Proteins • Cyclin is a cytoplasmic protein that fluctuates in concentration • Cyclin-Dependent Proteins: activate other proteins in the cell by phosphorylation (protein kinases) 11 What does MPF do? 12 Cdk Degraded cyclin G2 Cdk checkpoint Cyclin is degraded MPF Cyclin Molecular mechanisms that help regulate the cell cycle Stop and Go Signs: Internal and External Signals at the Checkpoints • An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase • 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 14 • Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing • Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide 15 • Cancer cells exhibit neither densitydependent inhibition nor anchorage dependence 16 Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). Normal mammalian cells 25 µm Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells