Cell Division & Cell Cycle
• http://www.youtube.com/watch?v=Q6ucKWIIFmg
Chapter 12: The Cell Cycle
http://highered.mcgraw-hill.com/olc/dl/120073/bio14.swf
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Omnis cellula e cellulaFrom every cell a cell – Rudolf Virchow
• Cell division: reproduction of cells• Cell cycle: life of a cell from the time it is first
formed from a dividing parent cell until it divides into 2 daughter cells
• Mitosis: nuclear division within a cell, followed by cytokinesis
• Cytokinesis: division of the cytoplasm– It is crucial that genetic material remains the same
from generation to generation
Mitosis• Mitosis functions in– Reproduction of single-celled organisms– Growth– Repair– Regeneration
• In contrast, meiosis produces gametes in sexually-reproducing organisms– Contains half the number of chromosomes of a
somatic cell
Organization of the Genetic Material• Cell division results in genetically
identical daughter cells– This requires DNA replication
followed by division of the nucleus• Genome: genetic content of the cell
– Prokaryotic cells have circular DNACircular DNA: a single long molecule
– Eukaryotic cells contain a number of DNA molecules specific to different speciesOne eukaryotic cell has about 2 meters of DNA
The DNA molecules in a cell are packaged into chromosomes– Eukaryotic chromosomes consist of chromatin, a complex of DNA
and protein that condenses during cell division– Euchromatin: less condensed and readily available for
transcription– Heterochromatin: highly compacted during interphase and
therefore not transcribed• Somatic cells: include all body cells, aside from
reproductive cells• Gametes: reproductive cells, include sperm and egg
Distribution of Chromosomes During Cell Division
• Non-dividing cells contain chromatin– In human cells there are 46 strands of chromatin, or
23 corresponding pairs of strands• Dividing cells contain chromosomes– Chromosomes becomes condensed prior to mitosis– Chomrosomes contain sister chromatids bound by a
centromere• Centromere contains kinetochore• Kinetochore: a structure of proteins associated with
specific sections of chromosomal DNA at the centromere
Chromosome Structure0.5 µm
Chromosomeduplication(including DNA synthesis)
Centromere
Separation of sister chromatids
Sisterchromatids
Centromeres Sister chromatids
A eukaryotic cell has multiplechromosomes, one of which is
represented here. Before duplication, each chromosome
has a single DNA molecule.
Once duplicated, a chromosomeconsists of two sister chromatids
connected at the centromere. Eachchromatid contains a copy of the
DNA molecule.
Mechanical processes separate the sister chromatids into two chromosomes and distribute
them to two daughter cells.
Figure 12.4
Mitotic Phase Alternates with Interphase in Cell Cycle
• Mitosis: M Phase includes mitosis and cytokinesis– Prophase– Prometaphase– Metaphase– Anaphase– Telophase
• Interphase: 90% of cell cycle; cell grows, producing organelles and proteins– G1: First gap– S: Synthesis, chromosome
replication– G2: Second gap; completes
preparation for cell division
INTERPHASE
G1
S(DNA synthesis)
G2Cyto
kinesis
Mitosis
MITOTIC(M) PHASE
In 24 hours…• Mitosis: 1 hour• G1: 5-6 hours (most variable)• S: 10-12 hours• G2: 4-6 hours
INTERPHASE
G1
S(DNA synthesis)
G2Cyto
kinesis
Mitosis
MITOTIC(M) PHASE
Mitotic Spindle is Necessary for Nuclear Division
• Mitotic spindle: used to segregate sister chromatids in anaphase
• Consists of microtubules and proteins
• Microtubules are able to change in length– Elongate by adding
Tubulin subunits– Shorten by loss of
Tubulin subunits
CentrosomeAster
Sisterchromatids
MetaphasePlate
Kinetochores
Overlappingnonkinetochoremicrotubules
Kinetochores microtubules
Centrosome
ChromosomesMicrotubules0.5 µm
1 µm
Mitotic Spindle• Interphase: the centrosome is
replicated and the two centrosomes remain paired near the nucleus– Centrosome or Microtubule Organizing
Center (MTOC): contains two centrioles• Prophase: spindle formation• Early Prophase: migration of
centrosomes to poles, spindle microtubules grow
• Late Prophase: centrosomes are at the poles, asters form – Aster: radial array of short microtubules– The mitotic spindle includes the
centrosomes, spindle microtubules and asters
Mitotic SpindlePrometaphase:• Kinetochore: protein structure
assiciated with specific sections of the chromosomal DNA at the centromere
• Kinetochore microtubules: attach kinetochore to spindle
• Metaphase Plate: created as microtubules attach to kinetochore, creation indicates Metaphase starts
Cellular Changes Indicate M- Phase Initiation
G2 of Interphase: nuclear envelope intact– Nucleus and nucleolus
present– Centrosome Replication
• Animal cells contain centrioles
– Chromosomes are not condensed and therefore not individually visible
Prophase• Nucleoli disappear• Chromosomes condense• Sister chromatids form– Two genetically identical
arms joined by the centromere and cohesin proteins
– Mitotic spindle forms using microtubules; asters form
– Centrosome migration as microtubules lengthen
Prometaphase
• Nuclear envelope fragments and microtubules invade nuclear area
• Nonkinetochore microtubules elongate
• Chromosomes condense further and gain kinetochore proteins
• Spindle fibers (microtubules) interact with kinetochores
Metaphase
• Longest stage of mitosis– Can last up to 20 minutes
• Metaphase plate: site of chormosome alignment
• Centrosomes are at poles• Sister chromatid
kinetochores attach to kinetochore microtubules
Anaphase• Shortest stage of mitosis• Cohesins between sister chromatids are
cleaved by enzymes– Sister chromatids are now separate
chromosomes• Spindle fibers shorten causing
chromosomes to move to opposite poles– Spindles shorten at kinetochore ends
according to Borisy et al.– Evidenced by Tubulin break down near
fluorescently-labeled kinetochores in pig kidney cells
• Nonkinetochore microtubules elongate cell
Telophase
• Daughter nuclei form in cell• Chromosomes loosen and
become less dense• Nucleoli reappear
Cytokinesis• Occurs in animal cells only• Relies on cleavage marked by a
cleavage currow• Cytoplasmic side of cleavage
furrow contains actin microfilaments and myosin– As the actin and myosin interact
the ring contracts and the cleavage furrow deepens
Cellular Division in Plant Cells• Plant cells form a cell plate following mitosis• Golgi vesicles contain cell wall materials and
migrate toward the center of the cell – forming the cell plate
Binary Fission
• Asexual eukaryotes can utilize mitosis for reproductive purposes – this is called binary fission
• Asexual prokaryotes perform binary fission that does not involve mitosis
Evolution of Mitosis• Some proteins were
highly conserved• In prokaryotes, protein
resembling eukaryotic actin may help with cell division– Tubulin-Like proteins may
help separate daughter cells
Attach to nuclear envelope
Reinforce spatial arrangement of nucleus
Spindle inside nucleus
Cell Cycle Regulation•Cytoplasmic regulators as shown in Mammalian cell Fusion experiment by Johnson and Rao (1970)
Cell Cycle Control System• Control systems vary cell to cell– Skin cells divide frequently, liver
cells only divide when needed (after injury), and nerve and muscle cells never divide
• Cytoplasmic molecules signal cell cycle as shown by Johnson and Rao
• Cell cycle events are regulated cyclicly– These are referred to as Cell
Cycle Checkpoints
Cell Cycle Control Systems• Cell Cycle Checkpoint: control
point in cell cycle where stop and go-ahead signals can regulate the cycle; relies on signal transduction pathways controlled by internal and external molecular signals– G1 checkpoint: acts as a
mammalian restriction point• “Go Signal” permits G1, S, G2 and M
• “Stop signal” causes G0 phase: non-dividing state, state of most human cells
– G2 checkpoint– M checkpoint
Cell Cycle Clock• The rate of cell cycle is
controlled by two proteins:– Cyclins– Cyclin-dependent
kinases (Cdks)
Cell Cycle Clock
• Kinases: activate or inactivate other proteins via phosphorylation– Inactive most of the time– Kinases are activated by cyclins
• Cyclins: regulatory proteins that have a cyclic (fluctuating) concentration in the cell
• Cyclin-dependent kinases (Cdks)– Activity fluctuates with cyclin concentration
Cell Cycle Clock• MPF: maturation-
promoting factor or M-phase promoting factor– MPF is a Cyclin-Cdk complex
• Triggers cell passage from G2 to M
• G2 checkpoint: As cyclin builds during G2 it binds with Cdk– Resulting MPF
phosphorylates proteins, initiating Mitosis
• During anaphase, MPF inhibits itself by destroying its own cyclin– Cdk persists in the cell
Stop and Go Signals
• Internal signals– M Phase checkpoint relies on kinetochore
signaling– Allows for enzymatic cleavage of cohesins
• External factors– Nutrients– Growth Factor Dependency– Density-dependent inhibition– Anchorage dependence
External Factors
• Growth Factor Dependency: over 50 known– Platelet-derived Growth Factor
(PDGF): made by platelets, required for fibroblast division in culture, used at injury sites in animals
– Fibroblasts have PDGF receptors • PDGF receptors are receptor tyrosine
kinases
• Density-Dependent Inhibition: corwded cells stop dividing– Cell surface protein binds the
adjoining cell sends a growth-inhibiting signal to cells
• Anchorage Dependence: cells require a growth substratum
Cancer Cells• Lack response to cell signals– Some can divide indefinitely (ex: HeLa cervical
cancer cells)– Cancer cells are not density or anchorage
dependent• Cancer starts with transformation– Normal cell becomes cancerous; this occurs
regularly and is usually amended by the immune system
– If not, the cancer cell divides and becomes a tumor
Cancer Cells
• Benign tumors: can be removed by surgery• Malignant tumors: invade surrounding tissues and organs, and
often metastasize– Metastasis: spread of cancer to far locations in the body
• Treatment options– Radiation: destroys cancer cells – Chemotherapy: medication that targets rapidly dividing cells (including
cancer cells)• Ex: Taxol – stops dividing cells by prevents microtubule depolymerization in
metaphase, but also affects cells that naturally divide often such as intestinal cells and skin cells of hair follicles