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BODY PROTEINEnzymeReceptor
HormoneGrowth Factor Immunoglobuln
Inter!eron" Interleu#n" $yto#ne%&he'on' molecule'H(%)*H$
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+TR,-T,R PROTEIN
+IF%T PROTEIN
F,NG+I PROTEIN
PE*BENT,-%N PROTEIN
DI+TRIB,+I PROTEIN
PE*ERI-+%%N PROTEIN
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Proten' are compo'e& o! 'ubunt' calle& amno ac&'
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Bo#ma . DN% a&alah Polymer &arDe'o/yrbonucleot&e 0Ba'a" zat Gula &an 1
atau lebh gugu' Pho'phat2 3at Gula . 4D45 De'o/yrbo'e 0Rbo'e2
I#atan N4Gly#o'&a antara De'o/yrbo'e0$12 &engan Pyrm&n 0N12 atau Purn 0N62
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% G $ G % T $ T G G
T $ G $ T % G % $ $
DN% Ba'e Parng
Double hel/ con''t' o! 5complmentary 'tran&' o! DN%7
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Gene'Gene' +egment' o! DN% co&e !or proten' 0or+egment' o! DN% co&e !or proten' 0or
part' o! proten'2part' o! proten'2
Each co&ng 'egment ' calle& a geneEach co&ng 'egment ' calle& a gene One gene co&e' one proten 0or part o!2One gene co&e' one proten 0or part o!2
Gene' contan the n!ormaton whchGene' contan the n!ormaton whch
ma#e' u' what we arema#e' u' what we are
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Gene Structure
E8ery three ba'e' o! DN% ' calle& a 9co&on:
Each co&on 'pec!e' an amno ac& whch
;on together to !orm the proten
eg %TG < methonne < +T%RT
T%% < +TOP
T%G < +TOP
TG% < +TOP
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Protein Synthesis -
Transcription
Each gene co&e' !or a proten
DN% 'en'e 'tran& act' a' template
an& ' 9tran'crbe&: nto me''enger
RN% 0mrror mage o! the DN% but
,racl n'tea& o! Thymne2
DN%
mRN%
% T $ G G
, % G $ $
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Protein Synthesis- Translation
Intron' are 'plce& out o! the mRN%
mRN% lea8e' the nucleu'
In the cytopla'm" rbo'ome' attach to themRN% en'urng the correct amno ac&" !or
each co&on" ' a&&e& to a growng chan o!
amno ac&' whch !orm' the re'ultng
proten7
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%mno ac& a''embly &urng tran'laton occur' on rbo'ome'=
tRN% 'er8e' a' the crucal a&aptor molecule
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Nu#leot&a 17 Nu#leot&a 57 Nu#leot&a >7
0?:2 0>:2, $ % G
, Phe +er Tyr $y' ,
, Phe +er Tyr $y' $
, (eu +er +TOP +TOP %
, (eu +er +TOP Trp G
$ (eu Pro H' %rg ,
$ (eu Pro H' %rg $
$ (eu Pro Gln %rg %
$ (eu Pro Gln %rg G
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, $ % G
% Ile Thr %'n +er ,
% Ile Thr %'n +er $
% Ile Thr (y' %rg %
% *et Thr (y' %rg G
G @al %la %'p Gly ,
G @al %la %'p Gly $
G @al %la Glu Gly %
G @al %la Glu Gly G
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DN% RN% Proten
tran'crpton
tran'laton
Proten +ynthe''
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*utaton'*utaton'% change n the DN% 'eAuence o! the% change n the DN% 'eAuence o! the
genegene
%ll cell' acAure mutaton' a' they%ll cell' acAure mutaton' a' they&8&e&8&e
rate o! appro/ 1rate o! appro/ 14C4C
per gene per cellper gene per cell
*utaton' can alter proten pro&uct o!*utaton' can alter proten pro&uct o!
DN%" 'top gene wor#ng or act8ateDN%" 'top gene wor#ng or act8ate
genegene
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Types of Mutation
Deleton 4 DN% m''ng
In'erton 4 e/tra DN% n'erte&
E/pan'on 0%mpl!caton2 4 DN%
repeat 'ze ha' ncrea'e&
Pont *utaton 4 change n one ba'e
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Types of Mutation(in coding sequence)
%G$ TT$ G%$ $$G l& type
%G$ T$G %$$ $G Deleton%G$ TT$ $G% $$$ G In'erton
%G$ TT$ TT$ G%$ $$G E/pan'on
%T$ TT$ G%$ $GG Pont mutaton
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POINT *,T%TION
,%%
0Termnaton $o&on2
, $%
0$o&on !or +erne2
, $ ,
0$o&on !or +erne2
$$ %
0$o&on !or Prolne2
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Cancer
Cancer is a group of diseases in whichgenetically damaged cells proliferateautonomously
The genetic damage consists of mutations(eg.point mutation deletion insertion) andchromosomal rearrangements or losses
Such changes result in the loss or altered
function of molecules in!ol!ed in cell growthor proliferation.
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Genes in Cancer
Mutations could affect Protooncogenesor Tumorsuppressor genes.
Protooncogenes code for a !ariety of
growth factors growth factor receptorsen"ymes or transcription factors thatpromote cell growth and#or cell di!ision.
Mutated !ersion of Protooncogenes(er$% ras &un fos myc etc) are called'ncogenes
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Genes in Cancer
Proto-oncogenes are acti!ated to
oncogenes $y !arious mechanisms.
. Promoter insertion . *nhancer insertion
+. Chromosomal translocations
,. Gene amplification . Point mutation
O $
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Oncogen $ancer
abl Tran'locaton $*(
myc Tran'locaton Bur#tt:' (ymphoma
erb B %mpl!caton Epthelcarcnoma"
%'trocytoma"
$a Oe'ophagu' neu %mpl!caton %&eno $a 0*ammae"
O8arum" Ga'ter2
myc %mpl!caton $a4 *ammae" (ung",teru'" Oe'
N4myc %mpl!caton Neurobla'toma" $a7Paru
Int45 %mpl!caton $a4Oe'ophagu'
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poptosis
Programme& cell &eath
Intracellular machnery re'pon'ble !or
apopto'' ' calle& ca'pa'e'7
$a'pa'e' +ynthe'ze& n the cell a' nact8e precur'or calle&
proca'pa'e'
,'ually act8ate& by clea8age at a'partc ac&' byother ca'pa'e'7
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Tumor suppressor genes
Play an mportant role n tumorgene''7
In8ol8e& n the control o! abnormal cell
prol!eraton7
(o'' or nact8aton . a''ocaton wth the
&e8elopment o! malgnancy7
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Tumor suppressor genes
The ma&ority of p+ mutations (/01) in$reast cancer are missense while 012nonsense mutations deletions insertions
P+ protein (34) normally inhi$its Cd3
(Cyclin dependent 3inase) en"ymes. 5ecent e!idence indicates that other
damaged or deleted Tumorsuppressorgenes may code for en"ymes in!ol!ed in46 5epair mechanisms.
7f 46 repair mechanisms are incompletea comple8 mechanism in!ol!ing P+ leadsto programmed cell death or poptosis
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Carcinogenics
5adiant energy Chemical compounds
9iruses ( 46 !irus56 !irus deno
!irus) These act $y causing mutations or $y
introducing no!el genes into cells
:amilial conditions (Tumor suppressor
genes) '8idati!e damage to 46 increase the
mutations rate
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Photodimeri"atio
n
|A
|C
|G
|T
|T
|C
|A
|T
T|
T|
G|A|
A|C|
G|
A|
|A
|C
|G
|C
|A
|T
T|
T|
G|
C|
G|
A|
thymine
dimer
;9 light*8posure to ;9 light
can cause ad&acent
thymines to
co!alently lin3.
This results in a
distortion of the 46
molecule and$rea3s the hydrogen
$onding with the
adenine.
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Carcinogenesis (ColorectalCancer)
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Tumor metastasis
Metastasis is the most dangerous
property of tumor cells
The cell grow as secondary tumors Many changes ha!e $een documented at
the surfaces of malignant cells
Some are2 alterations in transport
property diminished adhesion loss of
certain antigens etc.