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2005-2006 Biology is the only subject in which multiplication is the same thing as division… 2005-2006 The Cell Cycle: Cell Growth, Cell Division • You started as a cell smaller than a period at the end of a sentence… . 2005-2006 Where it all began… 2005-2006 And now look at you… How did you get from there to here? Getting from there to here… • continuity of life = reproduction of cells • reproduction • unicellular organisms • growth • repair & renew • Cell cycle • life of a cell from origin to division into 2 new daughter cells 2005-2006 • Cell division Getting the right stuff • exact copy of genetic material = DNA • this division step = mitosis • assortment of organelles & cytoplasm • this division step = cytokinesis chromosomes (stained orange) in kangaroo rat epithelial cell 2005-2006 • What is passed to daughter cells? Copying DNA • separates each copy to opposite ends of cell • splits into 2 daughter cells • human cell duplicates ~3 meters DNA • separates 2 copies so each daughter cell has complete identical copy • error rate = ~1 per 100 million bases • 3 billion base pairs • mammalian genome • ~30 errors per cell cycle • mutations 2005-2006 • Dividing cell duplicates DNA • DNA is organized in chromosomes • double helix DNA molecule • associated proteins = histone proteins • DNA-protein complex = chromatin • organized into long thin fiber 2005-2006 A bit about DNA Copying DNA with care… • coiling & folding to make a smaller package • from DNA to chromatin to highly condensed mitotic chromosome 2005-2006 • After DNA duplication chromatin condenses Chromosome chromosome consists of 2 sister chromatids narrow at their centromeres contain identical copies of the chromosome’s DNA 2005-2006 Duplicated M Mitosis G2 Gap 2 G1 Gap 1 • Cell has a “life cycle” cell is formed from a mitotic division cell grows & matures to divide again G1, S, G2, M epithelial cells, blood cells, stem cells S Synthesis cell grows & matures to never divide again liver cells G0 brain nerve cells 2005-2006 Cell cycle G0 Resting G2 Gap 2 • Phases of a dividing cell’s life • interphase S • cell grows Synthesis • replicates chromosomes • produces new organelles & biomolecules • mitotic phase • cell separates & divides chromosomes • mitosis • cell divides cytoplasm & organelles • cytokinesis G1 Gap 1 2005-2006 Cell Division cycle M Mitosis G0 Resting 2005-2006 Control of Cell Cycle Interphase • cell doing its “everyday job” • produce RNA, synthesize proteins • prepares for duplication if triggered • Characteristics • nucleus well-defined • DNA loosely packed in long chromatin fibers 2005-2006 • 90% of cell life cycle Interphase • G1 = 1st Gap • cell doing its “everyday job” • cell grows • S = DNA Synthesis • • copies chromosomes G2 = 2nd Gap • prepares for division • cell grows • produces organelles, proteins, membranes 2005-2006 • Divided into 3 phases: Interphase G2 • chromosome duplication complete • DNA loosely packed in long chromatin fibers • Prepares for mitosis • produces proteins & organelles 2005-2006 • Nucleus well-defined • copying cell’s DNA & dividing it between 2 daughter nuclei • Mitosis is divided into 4 phases • • • • prophase metaphase anaphase telophase 2005-2006 Mitosis 2005-2006 Overview • Chromatin (DNA) condenses • visible as chromosomes • chromatids • fibers extend from the centromeres • Centrioles move to opposite poles of cell • Fibers (microtubules) cross cell to form mitotic spindle • actin, myosin • Nucleolus disappears • Nuclear membrane breaks down 2005-2006 Prophase • Proteins attach to centromeres • creating kinetochores • Microtubules attach at kinetochores • connect centromeres to centrioles • Chromosomes begin moving 2005-2006 Prometaphase Kinetochore • microtubules attach to kinetochore proteins 2005-2006 • Each chromatid has own kinetochore proteins • Spindle fibers align chromosomes along the middle of cell • meta = middle • metaphase plate • helps to ensure chromosomes separate properly • so each new nucleus receives only 1 copy of each chromosome 2005-2006 Metaphase 2005-2006 • Sister chromatids separate at kinetochores • move to opposite poles • pulled at centromeres • pulled by motor proteins “walking”along microtubules • increased production of ATP by mitochondria • Poles move farther apart • polar microtubules lengthen 2005-2006 Anaphase • In anaphase, proteins holding together sister chromatids are inactivated • separate to become individual chromosomes 1 chromosome 2 chromatids 2 chromosomes 2005-2006 Separation of chromatids • Kinetochores use motor proteins that “walk” chromosome along attached microtubule • microtubule shortens by dismantling at kinetochore (chromosome) end 2005-2006 Chromosome movement • Chromosomes arrive at opposite poles • daughter nuclei form • nucleoli form • chromosomes disperse • no longer visible under light microscope • Spindle fibers disperse • Cytokinesis begins • cell division 2005-2006 Telophase Cytokinesis • cleavage furrow forms • ring of actin microfilaments forms around equator of cell • myosin proteins • tightens to form a cleavage furrow, which splits the cell in two • like tightening a draw string 2005-2006 • Animals 2005-2006 Cytokinesis in Animals QuickTime™ and a Animation decompressor are needed to see this picture. (play Cells Alive movie here) 2005-2006 Mitosis in whitefish blastula 2005-2006 Mitosis in animal cells Cytokinesis in Plants • vesicles move to equator line up & fuse to form 2 membranes = cell plate • derived from Golgi • new cell wall is laid down between membranes • new cell wall fuses with existing cell wall 2005-2006 • Plants 2005-2006 Cytokinesis in plant cell 2005-2006 Mitosis in plant cell 2005-2006 onion root tip • Mitosis in eukaryotes likely evolved from binary fission in bacteria • single circular chromosome • no membrane-bound organelles 2005-2006 Evolution of mitosis • Mechanisms intermediate between binary fission & mitosis seen in modern organisms • protists 2005-2006 Evolution of mitosis Dinoflagellates • “red tide” • bioluminescence 2005-2006 • algae Diatoms • marine • freshwater 2005-2006 • microscopic algae In order to divide: • • • • Reproductive signal Replication of DNA Segregation of DNA New material added to cell membrane for cytokinesis Prokaryotes • Binary fission • Signals are response to environment • Replication of DNA-1 chromosome, DNA folded on itself • Ori-where replication begins • Ter-where replication ends • Segregation of DNA-binding proteins • Cytokinesis-ring pinches in, then cell wall formed Eukaryotes • • • • Fertilized egg grows and develops Do not constantly divide Signal-not for single cell, but for individual Mitosis-clones • Very specialized-may lose ability to divide • Meiosis-gametes Control of Cell Division • G1S commitment to cell division is made • G2M cell enters mitosis • Regulated by Cyclins and Cyclin-dependent kinases • Kinases catalyze the transfer of a phosphate group from ATP to protein • Will change the protein shape Interactions • Binding with a cyclin activates a Cdk-allosteric interaction • Cyclin D-Cdk4 and Cyclin E-Cdk2 act during middle of G1 to move cell cycle past restriction point • Cyclin A—Cdk2 acts during S to stimulate DNA replication • Cyclin B-Cdk1 acts at G2-M boundary to begin mitosis • RB-normally inhibits cell cycle, but when it is phosphorylated-it is inhibited Growth factors • Some cells don’t move through cell cycles • Must be stimulated by growth factors 2005-2006
