Download Chapter 12: The Cell Cycle Asexual Cell Division • Creates

Chapter 12: The Cell Cycle
Asexual Cell Division
 Creates genetically identical daughter cells
o Single-celled = New offspring
o Multi-celled
 Growth & development
 Repair
Prokaryotes
 Reproduce via binary fission
o Circular DNA (genome) copied
 Starts at origin of replication (ORI)
o After replication, ORIs attaches to opposite ends of cell
o Cell elongates & chromosomes (XS) ‘grow’ apart
o Membrane pinches in & new cell wall formed
Eukaryote’s Cell Cycle
o Cell Division
 Mitosis – division of XS into 2 daughter nuclei
 Cytokinesis – division of organelles, cytoplasm, & cytosol b/w daughter cells
o Interphase…
 G1 Phase (First Gap)
 Cell size doubles, intense biochemistry time
o Increase in enzymes, ribosomes, mitochondria & other organelles
o Cytoskeletal elements from scratch
o Membranous structures develop from ER (e.g. Golgi, lysosomes)
o Mitochondria & chloroplasts replicate
o Centrioles replicate (if present)
 Chromosomes still chromatin
 S Phase (Synthesis)
 Begins preparation for cell division
 DNA molecules replicate & associated proteins produced
o Each XS now 2 diffuse strands
 Euchromatin – loosely packed
 Heterochromatin – tightly packed
 Centrioles continue to replicate
 G2 Phase (Second Gap)
 Final prep for cell division
o XS start to coil & condense (shorten/thicken)
o Centrioles completed
 2 pair slightly apart outside nucleus
o Microtubules begin to assemble for cell division
 Length of Time
 Some cells continuously divide
o Meristem of bean (19hrs)
 G1: 5hr, S: 7hr, G2: 5 hr, M: 2hr
o Mouse fibroblast (22hrs)
 G1: 9hr, S: 10hr, G2: 2hr, M:1hr
o Human Cell (24hrs)
 G1: 6hr, S: 10hr, G2: 5hr, M:1hr
 Some cells divide only under specific circumstances (liver)
 Others never divide after full differentiation (nerve, muscle)
 G0 phase – metabolically active, no mitosis ever (or unless urgent need)
o
Mitosis
 Chromosome Structure
 Called a Tetrad
 Pair of genetically identical sister chromatids (from S phase)
o Highly condensed chromatin
 Joined at centromere
o Region of DNA held together by cohesin proteins
o Has kinetochores – disc-like proteins that attach to MTs
 Mitotic Spindle
 Centrosome – MT organizing center at poles of cell
o Centrioles – function unknown
o Aster – astral rays radiate towards cell membrane
 May play role in anchorage
o Spindle Fibers = MTs
 Polar Fibers
 Run pole to metaphase plate (equator), don’t attach to XS
 Role in lengthening cell
 Kinetochore Fibers
 Pole to XS kinetochore
 When shortened, pulls XS apart
 Stages Of Mitosis
 Prophase
o XS are tightly coiled w/ sister chromatids joined together
o Condensation that began in G2 continues
o Nucleoli disappear
o Mitotic spindle begins to form & pushes centrosomes away from each other
toward poles of cell
 Prometaphase
o Nuclear envelope fragments
o Microtubules from spindle interact with chromosome’s kinetochores
 Kinetochore Fibers – attach from both sides to each chromatid
o Polar Fibers interact with microtubules from opposite pole
 Metaphase
o Chromosomes tugged back & forth by spindle fibers
o Precisely line up with centromeres along Metaphase plate (equator)
 Anaphase
o Centromeres divide, as cohesin proteins are cleaved by separase
o Chromatids are now pulled toward pole their spindle fiber attachment
 Now full chromosomes
o Cell elongates as polar fibers lengthen
o By the end, two poles have equivalent collections of chromosomes
o Shortest of mitotic phases
 Telophase
o Cell continues/finishes elongating
o Nuclei begin to form
 Nuclear Envelope remade w/ one pair of centrioles outside
 Chromatin loosens
 Nucleoli reappear
o Spindle taken apart & cytoskeleton reformed
 Cytokinesis
o Starts near end of telophase
o Cleavage Furrow in animals
 Cell membrane constricts around equator
 Actin fibers act with myosin to carry out a purse string-like action
 Pinches daughter cells in two
Cell Cycle Controls
 Checkpoints (stop & go signals) regulate cycle
 Internal Signals
o Key processes monitored for completion
 Extracellular Signals
o Hormones, touch, anchorage
 G1 Checkpoint
o Restriction point – most important for mammals
 If passed, cell will complete cell cycle & divide
 If not, cell exits cycle & enters G0
 Some return w/growth hormone
 Some never divide again
o Control Mechanisms
 Rhythmic fluctuations of control molecules regulate cycle
 Cyclin – protein w/ cyclical levels that bind kinases to activate them
 Protein Kinases – phosphorylating enzymes that can activate/deactivate
o aka cyclin-dependent kinase (Cdk)
o Abundant in cell, but inactive
 3 diff. Cdk complexes for G1 checkpoint
 G2 Checkpoint
o Cyclins build up during S & G2
o Bind to Cdk forming Maturation Promoting Factor (MPF)
o MPF phosphorylates many other kinases & proteins
 Triggers cell to initiate mitosis
 DNA condenses, spindle forms, nuclear envelope fragments
o Levels peak in metaphase, broken down in anaphase
 M Checkpoint
o Ensures that XS are attached to kinetochores at metaphase plate
o Once achieved…
 Enzyme cascade activates Separase
 Separase cleaves cohesion
 Sister chromatids separate
o Prevents uneven XS separation
 External Signals
o Growth Factors (50+ known)
 Proteins released by group of cells that stimulate other cells to divide
 Each cell type responds to different growth factors (or combos)
 Many cells won’t divide undergo ideal conditions w/o growth factors
 Platelet-derived Growth Factor (PDGF) stimulates division of fibroblasts
o Density-Dependent Inhibition
 Crowded cells stop dividing
 Growth factors & nutrients low
 Contact Inhibition
 Cells stop dividing when they touch (form single layer in culture)
 Remove neighbors = division
 Membrane proteins b/w cells interact to inhibit division
o Anchorage Dependence
 Most animal cells only divide if anchored to substratum
 Typically ECM of a tissue
 Control seems to come from connections b/w ECM, membrane proteins, & cytoskeletal
elements
Cancer Cells
 Exhibit uncontrolled division
o Loss of contact inhibition, density dependent inhibition, & anchorage dependence
 Usually immortal
 Lack cohesiveness to other cells
 Increased motility & mobility
 Sometimes signal others to divide
 Cancer Life Cycle
o Transformation
 Initiation – normal cell changed to cancerous
 Often killed by immune system
 Promotion – cancer cell proliferates
 Benign tumor – ‘abnormal’ cells stay at origin site (non-cancerous cells)
 Malignant tumor – cells can spread
o Metastasis – cancer cells have lost attachment to neighbors & spread via
lymph & blood vessels
 Escaping Cell Cycle
o Cells divide without growth factors
 Manufacture own factors
 Abnormal Pathway that can’t turn off
 Intrinsic or extrinsic
o Examples
 Tumor Suppressors
 Cause breaks in cell division
o Mutation = unregulated division
 Rb – retinoblastoma in eye
 p53 – prevents cells w/ DNA damage from dividing
 Oncogenes
 Normal genes involved in cell growth & division signalling
 Mutation can cause overproduction of products leading to cancer
 Ras – protein that signals cell division
o Mutated = uncontrolled division
 Viruses
 Rous Sarcoma Virus (chickens)
o Carries a gene making src protein
o Protein unregulated by animal cells
o Acts as an oncogene stimulating uncontrolled division
 Humans – Kaposi’s Sarcoma, Epstein-Barr, HPV, hepatitis
o SOMETIMES cause induction
 Treatments
o Excision – cut out
o Radiotherapy – radiation damages DNA beyond repair
o Chemotherapy – chemicals that inhibit cell division (esp. rapidly dividing cells) & kill
 Taxol – prevents MT disassembly
 Vinblasine & vincristine – prevent MT assembly & spindle formation
o Targeted therapy – drugs that attack specific cells