The Cell CycleThe Cell Cycle&&

The Process of Cell DivisionThe Process of Cell Division

Purpose of MitosisPurpose of Mitosis

• Growth Growth

• Embryonic developmentEmbryonic development

• Tissue repair Tissue repair

• Asexual reproductionAsexual reproduction

The Role of the The Role of the ChromosomeChromosome

Chromosomes are

a “scaffolding” that

hold, carry and

protect DNA

ChromosomesChromosomes• Exist as Exist as ChromatinChromatin for most of the cell cycle for most of the cell cycle

– Unwound, string-like (like a stretched out Slinky)Unwound, string-like (like a stretched out Slinky)

– DNA replication and RNA synthesis occur when like thisDNA replication and RNA synthesis occur when like this

• DNA in each cell is approximately DNA in each cell is approximately 2 meters2 meters long long

• Prior to cell divisionPrior to cell division, Chromatin begins to coil and thicken , Chromatin begins to coil and thicken ((super coilingsuper coiling))

• Now called Now called Chromosomes (sister chromatids)Chromosomes (sister chromatids)

– Initially joined all along their length by proteins called Initially joined all along their length by proteins called cohesins, later centromerecohesins, later centromere

• Human somatic cells have 46 chromosomesHuman somatic cells have 46 chromosomes

– Gametes have 23Gametes have 23

The Cell CycleThe Cell Cycle

• 2 general periods exist: 2 general periods exist: InterphaseInterphase and and mitotic (M) phasemitotic (M) phase

• 22-24 hour cycle22-24 hour cycle– 21 hours of Interphase (Growth)21 hours of Interphase (Growth)– 1 hour of Mitosis (Division)1 hour of Mitosis (Division)

The Cell CycleThe Cell Cycle

InterphaseInterphase

• 21 hours long21 hours long

• Three PhasesThree Phases– GG11, S, & G, S, & G22

• Cells grow in sizeCells grow in size

• Carries on metabolism ATP synthesis, Carries on metabolism ATP synthesis, excretion of waste, new organelle excretion of waste, new organelle synthesis, new proteinssynthesis, new proteins

• Chromosomes are duplicatedChromosomes are duplicated

GG11 (5-6 hrs long) (5-6 hrs long)(a.k.a.-Gap 1)(a.k.a.-Gap 1)

• Rapid growth and metabolic activityRapid growth and metabolic activity

• Multitudes of proteins being synthesizedMultitudes of proteins being synthesized

• Think “Magic ‘E’ word”Think “Magic ‘E’ word”

S (10-12 hours long)S (10-12 hours long)(a.k.a.-Synthesis)(a.k.a.-Synthesis)

• More growthMore growth

• DNA synthesis/replicationDNA synthesis/replication

GG22 (4-6 hrs long) (4-6 hrs long)(a.k.a.-Gap 2)(a.k.a.-Gap 2)

• GrowthGrowth

• Centrosomes replicateCentrosomes replicate– In animal cells, each In animal cells, each

centrosome has 2 centriolescentrosome has 2 centrioles

• Organelle manufacturingOrganelle manufacturing

• Final preparations for cell Final preparations for cell divisiondivision

GG00: Molecular Control of Cell : Molecular Control of Cell CycleCycle• Different cells = different cell cyclesDifferent cells = different cell cycles• Cytoplasmic signals seem to be most Cytoplasmic signals seem to be most

valid theory of cell division (think ECM; valid theory of cell division (think ECM; extra cellular matrix)extra cellular matrix)– Cell cycle control systemCell cycle control system

•Checkpoints dictate “stop and go”Checkpoints dictate “stop and go”– Can be internal and/or external signalsCan be internal and/or external signals

•GG11 checkpoint seems to be most important checkpoint seems to be most important– Go = GGo = G11, S, G, S, G22 and Mitosis and Mitosis– Stop = GStop = G0 0 (Most cells in the human body)(Most cells in the human body)

Cyclins and Cyclin-Dependent Cyclins and Cyclin-Dependent KinasesKinases

• Protein kinases (phosphotransferase)Protein kinases (phosphotransferase)– Enzymes that activate or inactivate other Enzymes that activate or inactivate other

proteins proteins •““Go” signal at GGo” signal at G11 and G and G22 checkpoints checkpoints

• Cyclins (think major milestones)Cyclins (think major milestones)– Proteins that attach to kinasesProteins that attach to kinases– Concentration fluctuates during cell cycleConcentration fluctuates during cell cycle

•Cyclin-dependent kinases (Cdks)Cyclin-dependent kinases (Cdks)

– Example of this relationship shown in Example of this relationship shown in Metaphase to Anaphase conversionMetaphase to Anaphase conversion

……continuedcontinued• Density-dependent inhibitionDensity-dependent inhibition

– Release of growth factors or growth inhibiting factorsRelease of growth factors or growth inhibiting factors•Surface proteins seem to be the receptors and Surface proteins seem to be the receptors and

messengers of this phenomenamessengers of this phenomena• Anchorage dependenceAnchorage dependence

– Substratum is essential for cell divisionSubstratum is essential for cell division• Cancer cells do not respond to these mechanismsCancer cells do not respond to these mechanisms

– HeLa cells (Henrietta Lacks, 1951)HeLa cells (Henrietta Lacks, 1951)– 20-50 cell divisions is the norm before autophagy20-50 cell divisions is the norm before autophagy– Transformation forms cancer cellsTransformation forms cancer cells

•Benign: Does not migrateBenign: Does not migrate•Malignant: affects multiple tissues/organsMalignant: affects multiple tissues/organs

– metastasismetastasis

Mitosis: Cell DivisionMitosis: Cell Division

• Approximately 1 hour longApproximately 1 hour long

• Has 5 phasesHas 5 phases– ProphaseProphase– PrometaphasePrometaphase– MetaphaseMetaphase– AnaphaseAnaphase– TelophaseTelophase

ProphaseProphase• Chromatin thickens into chromosomes Chromatin thickens into chromosomes

(supercoiling)(supercoiling)

– Sister ChromatidsSister Chromatids visible visible

• Held together by a centromereHeld together by a centromere

• Mitotic spindle begins to form (other Mitotic spindle begins to form (other microtubles dissociate to help form spindle)microtubles dissociate to help form spindle)

Prophase (continued)Prophase (continued)

• Nucleoli disappearNucleoli disappear

• CentriolesCentrioles migrate to opposite ends of the cell migrate to opposite ends of the cell– Spindle begins to form (cage-like structure, “aster”)Spindle begins to form (cage-like structure, “aster”)

PrometaphasePrometaphase

• Nuclear envelope fragementsNuclear envelope fragements

• Microtubles (spindle makes its way Microtubles (spindle makes its way towards nuclear region)towards nuclear region)

• Kinetochore present on each sister Kinetochore present on each sister chromatidchromatid

• Microtubels attach to kinetochore Microtubels attach to kinetochore and begin to loosen sister chromatidsand begin to loosen sister chromatids

MetaphaseMetaphase• Longest phase of mitosis (20 minutes)Longest phase of mitosis (20 minutes)

• Centrosomes at opposite polesCentrosomes at opposite poles

• Spindle arranges the chromosomes at Spindle arranges the chromosomes at the equatorial plane of cellthe equatorial plane of cell

• Chromosomes are fully attached to Chromosomes are fully attached to micortubles at kinetochoremicortubles at kinetochore

AnaphaseAnaphase• Shortest stageShortest stage

• Sister Sister chromatidschromatids separate via cohesin separate via cohesin separationseparation

• Microtubles begin dissociating, moving Microtubles begin dissociating, moving chromosomes to poleschromosomes to poles

• Cell lengthens as structural microtubles Cell lengthens as structural microtubles lengthenlengthen

TelophaseTelophase• Chromatids reach opposite ends of the cellChromatids reach opposite ends of the cell

• Nucleus and nucleolus form (nucleus via ER)Nucleus and nucleolus form (nucleus via ER)

• ChromosomesChromosomes lengthen into lengthen into chromatinchromatin againagain

• Spindle breaks downSpindle breaks down

• Plasma membrane begins to separate Plasma membrane begins to separate ((cytokinesiscytokinesis))– Animal cells pinch (cleavage furrow)Animal cells pinch (cleavage furrow)– Plant cells form new cell wallPlant cells form new cell wall

Telophase in plant and animal Telophase in plant and animal cellscells

Identical OffspringIdentical Offspring

• Asexual reproduction results in Asexual reproduction results in offspring “identical” to their parentsoffspring “identical” to their parents

• Types of asexual reproduction:Types of asexual reproduction:•Binary FissionBinary Fission

•BuddingBudding

•Spore FormationSpore Formation

•RegenerationRegeneration

•Vegetative ReproductionVegetative Reproduction

Binary FissionBinary Fission• Parent cell increases in size and splits into two Parent cell increases in size and splits into two

equal but smaller partsequal but smaller parts

• No parent cell is leftNo parent cell is left

• Occurs in single-celled organisms: amoeba, Occurs in single-celled organisms: amoeba, protozoa and certain algaeprotozoa and certain algae

• Prokaryotes (bacteria and archea) divide via Prokaryotes (bacteria and archea) divide via binary fission without mitosisbinary fission without mitosis

• One gene containing chromosomeOne gene containing chromosome– Origin of replicationOrigin of replication– Cell elongates and separates (tubulin? Actin?)Cell elongates and separates (tubulin? Actin?)

Bacteria & Protozoa Binary Bacteria & Protozoa Binary FissionFission

Evolutionary MitosisEvolutionary Mitosis

• Ancestral mechanisms remain intactAncestral mechanisms remain intact– Dinoflagellates: Replicated Dinoflagellates: Replicated

chromosomes attach to nuclear chromosomes attach to nuclear envelope and separate with nuclear envelope and separate with nuclear divisiondivision

– Diatoms and Yeasts: Spindle within Diatoms and Yeasts: Spindle within nucleus separates chromosomesnucleus separates chromosomes