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THE CELL CYCLE
IPMAT Regulation &
Its Lifespan Implication
Why Do Cells Divide?
Why Do Cells Divide?

Reproduction
– Binary Fission in bacteria

Tissue Growth
– Growth in multicellular organisms = more
cells not larger cells
Tissue Repair
 Maintain High Surface Area:Volume

– High volume = low efficiency
Parts in the Process:
Chromosomes
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:
Centrioles & The MTOC
http://sparkleberrysprings.com/v-web/b2/images/lotc/centriole14.jpg
Parts in the Process:
Spindle Fibers & Kinetochores
http://www.nikonsmallworld.com/gallery.php?grouping=year&year=2004&imagepos=18
Parts in the Process

Centrioles
– animal cells only
– MT
– spindle fiber organization

www.cellsalive.com
Centrosomes
– plant & animal cells
– AKA MTOC’s
http://osumolgen.siteturbine.com/sites/osumolgen/images/met3.jpg
Parts in the Process

Chromosomes
– Super-coiled DNA
– centromeres

Spindle 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 Cycle

Interphase can be divided into 3 main
substages:
– G1 – Gap 1 - period of growth
– S – Synthesis – DNA is copied (synthesized)
– G2 – Gap 2 – preparation for division
The Cell Cycle (continued)

Following G2 of Interphase, mitosis
(M-phase) carries out division:
– Prophase
– Metaphase
– Anaphase
– Telophase & Cytokinesis
http://www.biology.iupui.edu/biocourses/N100/2k4ch8mit
osisnotes.html
Prophase
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
Metaphase
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
Anaphase
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 & Cytokinesis

Telophase complete division of nucleus
– Spindle fibers disappear
– Nuclear membranes reappear

Cytokinesis complete division of
cytoplasm
– Cleavage furrow in animals
– Cell plate in plants
Plant Animation
Animal Mitosis
http://iknow.net/CDROMs/cell_cdrom/index.html
http://www.cbp.pitt.edu/faculty/yong_wan/index.html
Asymmetric 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 Cycle
G0
 Checkpoints
 Apoptosis

– Damage Prevention
– Developmental

Oncogenes
– Mitosis accelerators

Tumor Suppressor Genes
– Mitosis brakes
G0 – Exit From the Cell Cycle
temporary (wbc’s) or permanent (nerve)
 Cancer cells do not ever enter G0

Checkpoints in the Cell Cycle
G1, S, and M occur when cyclins
(proteins) bind & activate kinases.
 Kinases phosphorylate compounds
necessary for division.
 kinases blocked if damage detected @
G1, S, or M checkpoints.

MAD
p53
ATM
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellCycle.html
DNA Damage Detection

G1
– p53, 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

S
– ATM detects DNA damage, helps p53 send
irreparably damaged cells to death, & maintains
telomere length

M
– MAD stops mitosis if problems w/ microtubles in
spindle fiber formation
APOPTOSIS
Programmed Cell Death
Definition

Mechanism of normal, controlled death
by:
– DNA fragmentation
– Cytoplasm shrinkage
– Membrane blebbing
Cellular “suicide”
 No spillage or damage to nearby cells
 No inflammatory response

http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/apoptosisvideo.ht
ml
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?

Development
– Mouse paws (and human hands) use cell
death to form digits.
Death 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 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 Cancer

Oncogenes
– Genes known to speed up mitosis
– Mitosis accelerators when ON
(phosphorylation)
– Cancer results if ON when should be OFF

Tumor Suppressor Genes
– Mitosis brakes
– Tumors result if OFF when should be ON
Can a Cell Divide Forever?

Normal Cells – NO
– Telomeres, 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?

Cancer Cells – YES
– Telomerase is ON
• Enzyme repairs telomeres after each division

Embryonic Stem Cells – YES
– Fountain of Youth lies in harnessing antiaging powers of telomerase w/o risk of
cancer
NO EASY TASK
www.hybridmedicalanimation.com
http://www.ellisonfoundation.org/images/pfbs/p018_telomeres.jpg
The Cell Cycle
http://bhs.smuhsd.org/bhsnew/academicprog/science/vaughn/Student%20Projects/Paul%20&%20Marcus/Cell_Replication.html