mitosis regulation
TRANSCRIPT
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AP Biology 2006-2007
Regulation of Cell Division
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Coordination of cell division
A multicellular organism needs tocoordinate cell division across
different tissues & organsu
critical for normal growt!develo"ment & maintenance coordinate timing of
cell division
coordinate rates ofcell division
not all cells can ave te
same cell cycle
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#2
$ #%
meta"ase"ro"ase
ana"asetelo"ase
inter"ase '#%! $! #2"ases(
mitosis '(
cyto)inesis 'C(
C
*re+uency of cell division varies ,y cell ty"eu em,ryo
cell cycle 20 minute
u s)in cells
divide fre+uently trougout life %2-2. ours cycle
u liver cells retain a,ility to divide! ,ut )ee" it in reserve
divide once every year or two
u mature nerve cells & muscle cells do not divide at all after maturity
"ermanently in #0
*re+uency of cell division
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Cec)"oint control system
Cec)"ointsu cell cycle controlled ,y $/P& #/
cemical signals at critical "oints
u signals indicate if )ey cellular"rocesses ave ,eencom"leted correctly
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Cec)"oint control system
ma3or cec)"oints4u #%5$
can DA syntesis ,egin
u #25
as DA syntesis ,eencom"leted correctly
commitment to mitosis
u s"indle cec)"oint
are all cromosomesattaced to s"indle
can sister cromatidsse"arate correctly
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#%5$ cec)"oint
#%5$ cec)"oint is most criticalu "rimary decision "oint
8restriction "oint9
u
if cell receives 8#/9 signal! it divides internal signals4 cell growt 'si:e(! cell
nutrition
e;ternal signals4 8growt factors9
u
if cell does notreceivesignal! it e;its cycle &
switces to #0"ase
non-dividing! wor)ing state
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#0"ase
&
&itosis
#%
#a" %
#0
Resting
#2
#a" 2
$
$yntesis
#0"aseu non-dividing! differentiated state
u most uman cells in #0"ase
liver cells in #0! ,ut can ,e
8called ,ac)9 to
cell cycle ,y
e;ternal cues nerve & muscle cells
igly s"eciali:ed
arrested in #0
& can
never divide
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8#o-aead9signals
Protein signals tat "romote cell growt& divisionu internal signals
8"romoting factors9
u e;ternal signals
8growt factors9
Primary mecanism of controlu "os"orylation
)inaseen:ymes
eiter activates or inactivates cell
signals
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Cell cycle signals
Cell cycle controlsucyclins
regulatory "roteins
levels cycle in te cell
uCd)1s cyclin-de"endent )inases
"os"orylates cellular "roteins
wactivates or inactivates "roteinsuCd)-cyclin com"le;
triggers "assage troug differentstages of cell cycle
activated Cd)
inactivated Cd)
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Cyclins & Cd)s
=nteraction of Cd)1s & different cyclins triggers testages of te cell cycleu
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Cd) 5 #%cyclin
Cd) 5 #2cyclin 'P*(
#2
$
#%
C
#25 cec)"oint
#%5 $ cec)"oint
APC
Active=nactive
Active=nactive
=nactive
Active
mitosis
cyto)inesis
P*> itosis
Promoting *actor
APC> Ana"asePromoting Com"le;
Re"lication com"leted
DA integrity
Cromosomes attacedat meta"ase "late
$"indle cec)"oint
#rowt factors
utritional state of cell$i:e of cell
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Cyclin & Cyclin-de"endent )inases
CD?s & cyclin drive cell fromone "ase to ne;t in cell cycle
u "ro"er regulation of cell
cycle is so )ey to life
tat te genes for
tese regulatory"roteins ave ,een
igly conserved
troug
evolution
u te genes are ,asically
te same in yeast!
insects! "lants &
animals 'including
umans(
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@;ternal signals
#rowt factorsu coordination ,etween cells
u "rotein signals released ,y ,ody cellstat stimulate oter cells to divide density-de"endent ini,ition
w crowded cells sto" dividing
w eac cell ,inds a ,it of growt factorn not enoug activator left to
trigger division in any onecell
ancorage de"endence
w to divide cells must ,e attaced to asu,strate
n 8touc sensor9 rece"tors
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@2*
nucleuscyto"lasm
cell division
nuclear mem,rane
growt factor
"rotein )inasecascade
nuclear "ore
cromosome
Cd)cell surface
rece"tor
P
P
P
P
P
@2*R
,
R,
#rowt factor signals
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@;am"le of a #rowt *actor
Platelet Derived #rowt *actor 'PD#*(u made ,y "latelets in ,lood clots
u ,inding of PD#* to cell rece"tors stimulates cell
division in fi,ro,last 'connective tissue( eal wounds
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#rowt *actors and Cancer
#rowt factors can create cancersu "roto-oncogenes
normal growt factor genes tat
,ecome oncogenes 'cancer-causing(
wen mutated
stimulates cell growt
if switced 8/9can cause cancer
e;am"le4 RA$ 'activates cyclins(
u tumor-su""ressor genes ini,its cell division
if switced 8/**9can cause cancer
e;am"le4 "
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Cancer & Cell #rowt
Cancer is essentially a failureof cell division controlu unrestrained! uncontrolled cell growt
at control is lostu lose cec)"oint sto"s
u gene ""lays a )ey role in #%5$ restriction "oint
" "rotein alts cell division if it detects damaged DAw o"tions4
n stimulates re"air en:ymes to fi; DAn forces cell into #0resting stage
n )ee"s cell in #%arrest
n causes a"o"tosis of damaged cell
Acancers ave to sut down " activity
" discovered at $tony Broo) ,y Dr Arnold evine
p53 is theCell Cycle
Enforcer
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DA damage is caused,y eat! radiation! orcemicals
" allows cells
wit re"airedDA to divide
$te" %
DA damage iscaused ,y eat!radiation! or
cemicals
$te" % $te" 2
Damaged cells continue to divide
=f oter damage accumulates! tecell can turn cancerous
$te"
" triggers te destructionof cells damaged ,eyond re"air
AB/RA"
/RA"
a,normal
" "rotein
cancercell
$te" e " "rotein fails to sto"cell division and re"air DACell divides witout re"air to
damaged DA
Cell division sto"s! and" triggers en:ymes tore"air damaged region
$te" 2
DA re"air en:yme"
"rotein"
"rotein
" E master regulator gene
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Develo"ment of Cancer
Cancer develo"s only after a cell e;"eriencesF6 )ey mutations '8its9(u unlimited growt
turn ongrowt "romoter genes
u
ignore cec)"oints turn offtumor su""ressor genes '"(u esca"e a"o"tosis
turn offsuicide genes
u immortality > unlimited divisions
turn oncromosome maintenance genesu "romotes ,lood vessel growt
turn on,lood vessel growt genes
u overcome ancor & density de"endence
turn offtouc-sensor gene
It1s like anout of control
car!
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at causes tese 8its9
utations in cells can ,e triggered ,yu GH radiation
u cemical
e;"osure
u radiation
e;"osure
u eat
u cigarette smo)e
u "ollution
u
ageu genetics
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umors
ass of a,normal cellsu Benign tumor
a,normal cells remain at original site as alum"w " as alted cell divisions
most do not cause serious "ro,lems &can ,e removed ,y surgery
u alignant tumors cells leave original site
wlose attacment to near,y cells
w carried ,y ,lood & lym" system to otertissues
w start more tumors >metastasis
im"air functions of organs trougout ,ody
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raditional treatments for cancers
reatments target ra"idly dividing cellsu ig-energy radiation )ills ra"idly dividing cells
u cemotera"y sto" DA re"lication
sto" mitosis & cyto)inesis
sto" ,lood vessel growt