Regulation of Cell Division

AP Biology

2006-2007

Coordination of cell division A multicellular organism needs to

coordinate cell division across different tissues & organs
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critical for normal growt ! develo"ment & maintenance

coordinate timing of

cell division coordinate rates of cell division not all cells can ave t e same cell cycle
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*re+uency of cell division

*re+uency of cell division varies ,y cell ty"e
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em,ryo
cell cycle - 20 minute

s)in cells
divide fre+uently t roug out life %2-2. ours cycle

liver cells mature nerve cells & muscle cells #

2

retain a,ility to divide! ,ut )ee" it in reserve & meta" ase ana" ase divide once every year or two telo" "ro" ase
C

ase

do not divide at all after maturity inter" ase '#%! $! #2 " "ermanently in #0 mitosis '&(
$ cyto)inesis 'C(

ases( #%

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/verview of Cell Cycle Control 0wo irreversi,le "oints in cell cycle

re"lication of genetic material u se"aration of sister c romatids
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There1s no turning back, now!

C ec)"oints
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"rocess is assessed & "ossi,ly alted

sister c romatids

centromere

dou,le-stranded c romosomes

single-stranded AP Biology c romosomes

C ec)"oint control system C ec)"oints

cell cycle controlled ,y $0/P & #/ c emical signals at critical "oints u signals indicate if )ey cellular "rocesses ave ,een com"leted correctly
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C ec)"oint control system

2 ma3or c ec)"oints4
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#%5$
can D6A synt esis ,egin7

#25&
as D6A synt esis ,een

com"leted correctly7 commitment to mitosis

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s"indle c ec)"oint
are all c romosomes

attac ed to s"indle7 can sister c romatids se"arate correctly7

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#%5$ c ec)"oint
#%5$ c ec)"oint is most critical
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"rimary decision "oint

8restriction "oint9

if cell receives 8#/9 signal! it divides

internal signals4 cell growt 'si:e(! cell

nutrition e;ternal signals4 8growt factors9

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if cell does not receive signal! it e;its cycle & switc es to #0 " ase
non-dividing! wor)ing state

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#0 " ase #0 " ase

non-dividing! differentiated state u most uman cells in # " ase 0
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liver cells

& &itosis #2 #a" 2

in #0! ,ut can ,e

#% #a" %

$ $ynt esis

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8called ,ac)9 to cell cycle ,y e;ternal cues nerve & muscle cells #0 Resting ig ly s"eciali:ed arrested in #0 & can never divide

Activation of cell division <ow do cells )now w en to divide7

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cell communication signals

c emical signals in cyto"lasm give cue signals usually mean "roteins

w activators w in i,itors

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e;"erimental evidence4 Can you e;"lain t is7

8#o-a ead9 signals Protein signals t at "romote cell growt

& division
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internal signals
8"romoting factors9

e;ternal signals
8growt factors9

Primary mec anism of control

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" os" orylation

)inase en:ymes eit er activates or inactivates cell

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signals

inactivated Cd)

Cell cycle signals Cell cycle controls

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cyclins
regulatory "roteins levels cycle in t e cell

Cd)1s

cyclin-de"endent )inases " os" orylates cellular "roteins w activates or inactivates "roteins
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activated Cd)

Cd)-cyclin com"le;
triggers "assage t roug different

stages of cell cycle

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Cyclins & Cd)s

=nteraction of Cd)1s & different cyclins triggers t e
stages of t e cell cycle
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#2 5 & c ec)"oint
Re"lication com"leted D6A integrity Active =nactive

$"indle c ec)"oint
C romosomes attac ed at meta" ase "late =nactive Cd) 5 #2 cyclin '&P*( Active

&

APC

cyto)inesis

#2

mitosis

#% $
&P* > &itosis Promoting *actor APC > Ana" ase AP Biology Promoting Com"le; Cd) 5 #% cyclin Active

=nactive

#% 5 $ c ec)"oint

#rowt factors 6utritional state of cell $i:e of cell

Cyclin & Cyclin-de"endent )inases

CD?s & cyclin drive cell from
"ro"er regulation of cell cycle is so )ey to life t at t e genes for t ese regulatory "roteins ave ,een ig ly conserved t roug evolution u t e genes are ,asically t e same in yeast! insects! "lants & animals 'including umans(
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one " ase to ne;t in cell cycle

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@;ternal signals
#rowt factors
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coordination ,etween cells "rotein signals released ,y ,ody cells t at stimulate ot er cells to divide
density-de"endent in i,ition w crowded cells sto" dividing w eac cell ,inds a ,it of growt factor n not enoug activator left to trigger division in any one cell anc orage de"endence w to divide cells must ,e attac ed to a su,strate n 8touc sensor9 rece"tors

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#rowt factor signals

growt factor

nuclear "ore nuclear mem,rane P P

cell division
Cd) P
@2*

cell surface rece"tor "rotein )inase cascade

P

R, *
@2

c romosome P
R,

APcyto"lasm Biology

nucleus

@;am"le of a #rowt *actor

Platelet Derived #rowt *actor 'PD#*(
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made ,y "latelets in ,lood clots ,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 cancers

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"roto-oncogenes
normal growt factor genes t at

,ecome oncogenes 'cancer-causing( w en mutated stimulates cell growt if switc ed 8/69 can cause cancer e;am"le4 RA$ 'activates cyclins(
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tumor-su""ressor genes
in i,its cell division if switc ed 8/**9 can cause cancer

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e;am"le4 "A2

Cancer & Cell #rowt

Cancer is essentially a failure
of cell division control
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unrestrained! uncontrolled cell growt lose c ec)"oint sto"s gene "A2 "lays a )ey role in #%5$ restriction "oint
"A2 "rotein alts cell division if it detects damaged D6A w o"tions4 n stimulates re"air en:ymes to fi; D6A n forces cell into # resting stage 0 n )ee"s cell in # arrest % n causes a"o"tosis of damaged cell ACC cancers ave to s ut down "A2 activity

B at control is lost7
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p53 is the Cell Cycle Enforcer

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"A2 discovered at $tony Broo) ,y DrD Arnold Cevine

"A2 E master regulator gene

6/R&AC "A2
"A2 allows cells wit re"aired D6A to divideD "A2 "rotein D6A re"air en:yme "A2 "rotein

$te" %
D6A damage is caused ,y eat! radiation! or c emicalsD

$te" 2
Cell division sto"s! and "A2 triggers en:ymes to re"air damaged regionD

$te" 2
"A2 triggers t e destruction of cells damaged ,eyond re"airD

AB6/R&AC "A2
a,normal "A2 "rotein

$te" %
D6A damage is caused ,y eat! radiation! or emicalsD AP c Biology

$te" 2
0 e "A2 "rotein fails to sto" cell division and re"air D6AD Cell divides wit out re"air to damaged D6AD

cancer cell

$te" 2
Damaged cells continue to divideD =f ot er damage accumulates! t e cell can turn cancerousD

Develo"ment of Cancer
Cancer develo"s only after a cell e;"eriences
F6 )ey mutations '8 its9(
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unlimited growt
turn on growt "romoter genes

ignore c ec)"oints
turn off tumor su""ressor genes '"A2(

esca"e a"o"tosis
It1s like an immortality > unlimited divisions out of control turn on c romosome maintenance genes car!

turn off suicide genes

"romotes ,lood vessel growt

turn on ,lood vessel growt genes

overcome anc or & density de"endence

turn off touc -sensor gene

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B at causes t ese 8 its97 &utations in cells can ,e triggered ,y

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GH radiation c emical e;"osure radiation e;"osure eat

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cigarette smo)e "ollution age genetics

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0umors
&ass of a,normal cells
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Benign tumor
a,normal cells remain at original site as a

lum"

w "A2 as alted cell divisions

most do not cause serious "ro,lems &

can ,e removed ,y surgery

&alignant tumors
cells leave original site w lose attac ment to near,y cells w carried ,y ,lood & lym" system to ot er
tissues w start more tumors > metastasis

im"air functions of organs t roug out ,ody

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0raditional treatments for cancers

0reatments target ra"idly dividing cells
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ig -energy radiation
)ills ra"idly dividing cells

c emot era"y
sto" D6A re"lication sto" mitosis & cyto)inesis sto" ,lood vessel growt

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