THE CELL CYCLE IPMAT Regulation & Its Lifespan Implication

THE CELL CYCLETHE CELL CYCLE

IPMAT Regulation & IPMAT Regulation &

Its Lifespan ImplicationIts Lifespan Implication

Why Do Cells Divide?Why Do Cells Divide?

Why Do Cells Divide?Why Do Cells Divide?

ReproductionReproduction– Binary Fission in bacteria

Tissue GrowthTissue Growth– Growth in multicellular organisms = more

cells not larger cells Tissue RepairTissue Repair Maintain High Surface Area:VolumeMaintain High Surface Area:Volume

– High volume = low efficiency

Parts in the Process:Parts in the Process: ChromosomesChromosomes

http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/cell.f04/cellf04.html http://mbbnet.umn.edu/icons/chromosome.jpeg

Parts in the Process:Parts in the Process: Centrioles & The MTOCCentrioles & The MTOC

http://sparkleberrysprings.com/v-web/b2/images/lotc/centriole14.jpg

Parts in the Process:Parts in the Process: Spindle Fibers & KinetochoresSpindle Fibers & Kinetochores

http://www.nikonsmallworld.com/gallery.php?grouping=year&year=2004&imagepos=18

Parts in the ProcessParts in the Process CentriolesCentrioles

– animal cells only– MT– spindle fiber organization

Centrosomes Centrosomes – plant & animal cells– AKA MTOC’s

www.cellsalive.com

http://osumolgen.siteturbine.com/sites/osumolgen/images/met3.jpg

Parts in the ProcessParts in the Process

ChromosomesChromosomes– Super-coiled DNA – centromeres

Spindle FibersSpindle Fibers– MT’s attached to centromeres @

kinetochore– Tracks for chromosome movement toward

centrioles @ poles

http://www2.geneticsolutions.com/PageReq?id=3844:1873

http://www2.geneticsolutions.com/PageReq?id=3844:1873

The Cell CycleThe Cell Cycle

IInterphase can be divided into 3 main substages: – GG11 – Gap 1 - period of growth

– SS – Synthesis – DNA is copied (synthesized)

– GG22 – Gap 2 – preparation for division

The Cell CycleThe Cell Cycle (continued) Following GG22 of IInterphase, mitosis

(M-phase) carries out division:– PProphase– MMetaphase– AAnaphase – TTelophase & Cytokinesis http://www.biology.iupui.edu/biocourses/

N100/2k4ch8mitosisnotes.html

ProphaseProphase Centrosomes to poles Nuclear membrane disappears Chromatin condenses to form

chromosomes

http://micro.magnet.fsu.edu/micro/gallery/mitosis/lateprophase.html http://www.dundee.ac.uk/biocentre/GRE%20Scientific%20images/pages/Prophase.htm

MetaphaseMetaphase Chromosomes in middle of cell Spindle fibers form Kinetochores attach to centromeres of

each chromatid

http://www.brown.edu/Courses/BI0020_Miller/images/metaphase-1.jpg http://www.pc.vccs.edu/biology-labmanual/lab7mitmei/whitefishmeta.jpg

AnaphaseAnaphase Sister chromatids separate Chromatids move to poles using

retreating spindle fibers (D.I.)

http://micro.magnet.fsu.edu/micro/gallery/mitosis/earlyanaphase.html http://content.answers.com/main/content/wp/en/thumb/3/38/300px-Anaphase-flourescent.jpg

Telophase & CytokinesisTelophase & Cytokinesis TelophaseTelophase complete division of nucleus

– Spindle fibers disappear– Nuclear membranes reappear

CytokinesisCytokinesis complete division of cytoplasm– Cleavage furrow in animals– Cell plate in plants

http://iknow.net/CDROMs/cell_cdrom/index.html

Plant Animation

Animal Mitosis

http://www.cbp.pitt.edu/faculty/yong_wan/index.html

Asymmetric DivisionAsymmetric Division Specialization of stem cells New daughter cells not identical

http://labshelf.com/stem-cells-treatments-research.html http://labshelf.com/stem-cells-treatments-research.html

Regulation of Cell CycleRegulation of Cell Cycle G0

Checkpoints Apoptosis

– Damage Prevention– Developmental

Oncogenes– Mitosis accelerators

Tumor Suppressor Genes– Mitosis brakes

GG00 – Exit From the Cell Cycle – Exit From the Cell Cycle temporary (wbc’s) or permanent (nerve) Cancer cells do not ever enter G0

Checkpoints in the Cell CycleCheckpoints in the Cell Cycle

GG11, SS, and MM occur when cyclinscyclins (proteins) bind & activate kinaseskinases.

Kinases phosphorylate compounds necessary for division.

kinases blocked if damage detected @ GG11, SS, or MM checkpoints.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellCycle.html

p53p53

ATMATM

MADMAD

DNA Damage DetectionDNA Damage Detection GG11

– p53p53, a tumor suppressor, checks for damage before DNA replication

– If damage cannot be repaired, p53 sends cell to to die so it cannot lead to cancer

– P53 mutations implicated in > ½ of all human cancers SS

– ATMATM detects DNA damage, helps p53 send irreparably damaged cells to death, & maintains telomere length

MM– MADMAD stops mitosis if problems w/ microtubles in spindle

fiber formation

APOPTOSISAPOPTOSIS

Programmed Cell Death

DefinitionDefinition Mechanism of normal, controlled death

by:– DNA fragmentation– Cytoplasm shrinkage– Membrane blebbing

Cellular “suicide” No spillage or damage to nearby cells No inflammatory responsehttp://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/apoptosisvideo.html

Is All Cell Death Equal?Is All Cell Death Equal?

Necrosis– Messy cell death usually due to injury– Cellular “homicide”– Cell contents come spilling out leading to an

inflammatory response. • Swelling• Redness• Fever

Why Suicide?Why Suicide?

Development– Mouse paws (and human hands) use cell

death to form digits.

Death As A Necessity For LifeDeath As A Necessity For Life

Immune system cells• Virally infected cells• Immune cells that don’t recognize “self”• Removal of cytotoxic T cells after infection is

conquered

DNA damaged cells• Sent to their death by p53 to prevent tumors

Disorders InvolvedDisorders Involved

Neurological disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases

• Too much apoptosis

Cancer• Not enough apoptosis

Cell Division Cell Death

Genes in CancerGenes in Cancer OncogenesOncogenes

– Genes known to speed up mitosis– Mitosis accelerators when ON

(phosphorylation)– Cancer results if ON when should be OFF

Tumor Suppressor GenesTumor Suppressor Genes– Mitosis brakes– Tumors result if OFF when should be ON

Can a Cell Divide Forever?Can a Cell Divide Forever?

Normal CellsNormal Cells – NONO– TelomeresTelomeres, buffer zones @ tips of each

chromosome, get shorter w/ each division– Cells die when telomeres gone

• EX: Aging effects are due to dead cells that can no longer be replaced

Can a Cell Divide Forever?Can a Cell Divide Forever? Cancer CellsCancer Cells – YESYES

– Telomerase is ON• Enzyme repairs telomeres after each division

Embryonic Stem CellsEmbryonic Stem Cells – YESYES– Fountain of Youth lies in harnessing anti-

aging powers of telomerase w/o risk of cancer

NO EASY TASKNO EASY TASK

www.hybridmedicalanimation.com http://www.ellisonfoundation.org/images/pfbs/p018_telomeres.jpg

The Cell CycleThe Cell Cycle

http://bhs.smuhsd.org/bhsnew/academicprog/science/vaughn/Student%20Projects/Paul%20&%20Marcus/Cell_Replication.html