THE CELL CYCLE

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Reproduction
2. Growth & Development
3. Tissue Renewal
1.
life of a cell from time it is 1st formed to
time it divides into 2 daughter cells
 in the process it passes along identical
genetic material

cells genetic information (DNA)
 2 m DNA in typical eukaryotic cell
 for cell to divide all the DNA must be
replicated then separate so each daughter
cell has complete genome

eukaryotic structure
 1 long DNA molecule associated
w/proteins = chromatin
 each has several 100 to thousands of genes
 associated proteins maintains structure of
chromosome & help control activity of
genes

somatic cells: all body cells except gametes
 gametes: reproductive cells, sperm & egg

2 main parts:
1. Interphase
 G1
 S
 G2
1. M-Phase
 Mitosis
 Cytokinesis

begins to form in cytoplasm during
prophase
 made up of microtubules (made of protein
tubulin) + associated proteins
 material for assemblage of microtubules
comes from disassembly of other
microtubules in cell

assembly of
microtubules begins
@ centrosome
 pair of centrioles @
center of centrosome
› not essential,
spindle forms if
destroyed

single centrosome duplicates during
interphase
 2 centrosome separate & move apart during
prophase  @ opposite poles by
prometaphase

Centrosomes
2. Spindle microtubules
3. Asters
1.

protein structure attached to centromere
that links each sister chromatid to mitotic
spindle
chromosomes 2 kinetochores face in
opposite directions
 spindles that attach to kinetochore in
prometaphase called kinetochore
microtubules
 #s attached vary by species

when 1 of chromosome’s kinetochore is
“captured” by microtubules the
chromosome begins to move toward the
pole from which those microtubules extend
 “tug-of-war” between 2 sides until @
metaphase all duplicated chromosomes on
plane midway between the spindle’s 2
poles

imaginary cell structure
 midway between 2 poles of spindle
 nonkinetochore microtubules elongate &
interact with other like kinetochores from
opposite pole

~90% of cell cycle
 3 parts


cell growth:
› size increases
› organelles made
chromosomes duplicated
 each chromosome made up of sister
chromatids with same genetic information

nuclear envelope intact
 1 or more nucleoli
 centrosomes duplicate

› 2 centrioles in each

duplicated chromosomes not yet
condensed
chromatin condenses into chromosomes
becoming visible
 nucleoli disappear
 mitotic spindle begins to form
 centrosomes move away from each other
(propelled partly by lengthening
microtubules between them)

nuclear envelope fragments
 microtubules from each centrosome now
invade nuclear space
 more condensation of chromatin 
chromosomes
 kinetochore on each sister chromatid
 kinetochore microtubules begin to attach
 nonkinetochore microtubules begin to
interact

centrosomes @ opposite poles
 chromosomes @ metaphase plate
 kinetochores of sister chromatids attached
to microtubules from opposite poles

shortest stage of mitosis
 begins when cohesin proteins are cleaved
allowing sister chromatids to separate (each
chromatid now a chromosome)
 each daughter chromosome moves toward
opposite poles as its kinetochore
microtubule shortens
 Cell elongates as nonkinetochore
microtubules lengthen
 @ end of anaphase each pole of cell has
complete set of chromosomes

2 daughter nuclei form
 nuclear envelopes form from fragments of
parent cell’s nuclear envelope
 nucleoli reappear
 chromosomes become less condensed
 remaining spindle microtubules
depolymerize
 Mitosis (nuclear division) is complete!

division of cytoplasm
 usually begins in telophase
 animal cells: cleavage furrow
 plant cells: cell plate
 ends with 2 daughter cells genetically
identical to parent cell

Animal Cells



Plant Cells


occurs by process known as cleavage
on cytoplasmic side ring of actin
microfilaments w/myosin molecules causes
ring to contract (like pulling a drawstring
cleavage furrow deepens until cell is
pinched in 2
during telophase, vesicles (containing cell
wall materials) from Golgi move along
microtubules to center of cell
contents of vesicles forms cell plate
asexual reproduction in prokaryotic cells
 single loop of DNA & associated proteins
carries most of genes
 No mitosis in prokaryotic cells
 amt of DNA in E. coli 500x length of the
cell so it must be highly coiled & folded

DNA begins replication @ specific spot:
origin of replication creating 2 pts of origin
 1 pt of origin moves to opposite end of cell
 as DNA replicates cell elongates  ~2x
 when DNA replication complete plasma
membrane pinches in 2
 each new cell has exact same DNA as
parent cell

unknowns:
 how pts of origin move (no microtubules)

› proteins similar to actin & tubulin identified

Some unicellular eukaryotes existing today
have mechanisms of cell division that may
resemble intermediate steps in the
evolution of mitosis
chromosomes attach to nuclear envelope
 nuclear envelope remains intact thru cell
division
 microtubules pass thru nucleus stabilizing
chromosome positions
 rest of cell division very like binary fission

unicellular
 nuclear envelopes remain intact
 spindle formed of microtubules inside
nucleus
 microtubules separate chromosomes
 nucleus then splits

 different
cell
types divide at
different rates
 all controlled by
regulation @
molecular level
a cyclically operating set of molecules in
the cell that
1. trigger
2. coordinate
 checkpoint: control pt where stop & go
signals can regulate cell cycle

have built-in stops that must be overridden by go signals
 most come from mechanisms w/in cell
 responsible for checking whether crucial
processes that should have occurred by that
pt. have been successfully completed
 ckpts. also register signals from outside cell

G1
2. G2
3. M phase
1.
“restriction point”
 seems to be most important in mammalian
cells
 If cell gets “go-ahead” here, it will likely
complete cell cycle

where cells “go” if not destined to divide
again
 most cells of human body are here

› some will never divide again
 neurons, muscle fibers
› others “called-back” when necessary
 liver

protein kinases
› enzymes that activate/ inactivate other proteins
by phosphorylating/dephosphorylating them
› some give “go-ahead” signals @ G1 & G2
› many always present in cytoplasm but usually
in inactive form
› activation involves being attached to a cyclin
called cyclin-dependent kinases or Cdks

their activity in cell fluxuates as
concentrations of its cyclin change
or MPFs
 triggers cell thru G2 checkpt  M phase
 2 actions:
1. directly as a kinase
2. indirectly by activating other kinases
 example: MPF phosporylates various
proteins that promote fragmentation of
nuclear envelope & contributes to
molecular events required for
chromosomes to condense


cyclin part of MPF destroyed

noncyclin part of MPF (the Cdk) persists in
the cell in its inactive form until it
associates with new cyclin molecules made
in next S & G2 phases
animal cells have @ least 3 Cdk proteins &
several different cyclins
 fluctuating activities of different Cdkcyclin complexes of major importance in
controlling stages of cell cycle
 http://highered.mcgrawhill.com/sites/9834092339/student_view0/ch
apter10/stimulation_of_cell_replication.ht
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
M-phase Checkpoint
 @ anaphase
 chromatids do not separate til all are
properly attached to spindle @ metaphase
plate
 when all attachments made  activation of
regulatory protein kinase  molecular
events that activates enzyme separase 
cuts cohesions  sister chromatids separate


Cell Cultures
› require specific nutrients in culture medium
› most types of mammalian cell cultures require
specific growth factors
Growth factor: protein released by certain cells
that stimulates other cells to divide
>50 discovered to date
PDGF
 made by plts
 CT cell, fibroblast has receptors for them
 when PDGF attached to receptor (tyrosine
kinase) signal transduction pathway
initiated that allows cells to pass G1
checkpoint
 this process used in wound healing

 another external
signal
 phenomena
noted: crowded
cells stop
dividing (contact
inhibition)

binding of a cell-surface protein to its
counterpart on adjoining cell sends a
growth-inhibiting signal to both cells
another external signal
 exhibited by most animal cells
 cells must be attached to something (side of
culture jar or extracellular matrix of a
tissue) to divide


Cancer Cells
› loss of contact inhibition
› if & when they stop dividing they stop @
random pts in cell cycle
› in culture they divide forever if supplied
with supply of nutrients
› do not have pathway  apoptosis
begins when a single cell undergoes
transformation (conversion of normal cell
 cancer cell)
 normally, immune system IDs one &
destroys it
 Benign tumors (kind) do not spread, most
surgically removed
 Malignant tumors (bad) spread to 1 or more
organs eventually destroying their function

excessive proliferation
 abnl #s of chromosomes
 metabolism altered
 changes on cell surface  lose attachments
to other cells or extracellular matrix 
nearby organ or blood/lymph vessels
(metastasis)
 may secrete signaling molecules  growth
of blood vessels toward cancer tumor


Radiation Therapy
› localized tumors
› damages DNA: cancer cells less likely able to
repair

Chemotherapy
› metastatic tumors (systemic therapy)
› drugs toxic to specific step in cell cycle
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