ASAM NUKLEAT

& SINTESIS
PROTEIN

dr. Husnul Kh, M.Sc

Bgn Biologi Kedokteran
FK.UNLAM
 pendahuluan
• Life depends on the ability of cells to store,
retrieve, and translate the genetic instructions
required to make and maintain a living organism.
• This hereditary information is passed on from a
cell to its daughter cells at cell division, and from
one generation of an organism to the next through
the organism’s reproductive cells.
• The instructions are stored within every living cell
as its genes, the information- containing elements
that determine the characteristics of a species as
a whole and of the individuals within it.
• A German chemist, Friedrich Miescher, discovered DNA in
1869, only four years after Mendel’s work was published.
• Miescher extracted a white substance from the nuclei of
human cells and fish sperm. The proportion of nitrogen and
phosphorus in the substance was different from that in
any other known constituent of cells, which convinced
Miescher that he had discovered a new biological substance.
• He called this substance “nuclein,” because it seemed to be
specifically associated with the nucleus.
Discovery of the Role of DNA

A. 1928 - Frederick Griffith discovers transformation in bacteria :

* discovered that “something” was able to transform harmless
(non – virulent) bacteria into harmful (virulent)
Discovery of the Role of DNA (cont’d)
B. 1944 -Oswald Avery
and colleagues show
that DNA can
transform bacteria
C. 1952 - Alfred Hershey and
Martha Chase use bacteriophage
to confirm that DNA is the
genetic material
Hershey-Chase Experiment: Infected cells make
more virus by injecting their DNA animation

1
Discovery of the Role of DNA (cont’d)
D. 1953 - James Watson and Francis Crick propose a
structural model for the DNA molecule
Based On:
1. X-Ray crystallography images
prepared by Maurice Wilkins
and Rosalind Franklin
2. Chargraff’s Rule:
# of Adenines = # of Thymines
# Guanines = # of Cytosines
Two types of nucleic acid are found
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)

© 2007 Paul Billiet ODWS

 The distribution of nucleic acids
in the eukaryotic cell
• DNA is found in the nucleus
with small amounts in mitochondria and
chloroplasts
• RNA is found throughout the cell

© 2007 Paul Billiet ODWS

 NUCLEIC ACID STRUCTURE
• Nucleic acids are polynucleotides
• Their building blocks are nucleotides

© 2007 Paul Billiet ODWS

 NUCLEOTIDE STRUCTURE

PHOSPATE SUGAR BASE

Ribose or PURINES PYRIMIDINES
Deoxyribose
Adenine (A) Cytocine (C)
Guanine(G) Thymine (T)
Uracil (U)

NUCLEOTIDE
© 2007 Paul Billiet ODWS
 Ribose is a pentose

C5

C4 C1

C3 C2

© 2007 Paul Billiet ODWS

 Spot the difference

RIBOSE DEOXYRIBOSE

CH2OH CH2OH
O OH O OH

C C C C

H H H H H H H H

C C C C

OH OH OH H
© 2007 Paul Billiet ODWS
 P

THE SUGAR-PHOSPHATE
BACKBONE P

• The nucleotides are all

orientated in the same P

direction
• The phosphate group joins P

the 3rd Carbon of one sugar

to the 5th Carbon of the next P

in line.
P

© 2007 Paul Billiet ODWS

 P
G

ADDING IN THE BASES P

C

• The bases are

P
attached to the 1st C
Carbon
• Their order is P
A
important
It determines the P

genetic information T

of the molecule P
© 2007 Paul Billiet ODWS
T
 Hydrogen bonds

P
G C
DNA IS MADE OF P
TWO STRANDS OF P
C
POLYNUCLEOTIDE G
P
P
C G
P
P
A T
P
P
T A
P
P
T A
© 2007 Paul Billiet ODWS
P
 STRUKTUR DNA

“Double heliks” ditemukan oleh Watson dan Crick

(1953)
Merupakan suatu polinukleotida yang terdiri dari
– Gula pentosa : deoksiribosa
– Pospat : PO4
– Basa nitrogen :
• Pirimidin : sitosin (S) – Timin (T)
• Purin : Adenin (A) – Guanin (G)
Kedua basa nitrogen berikatan melalui ikatan
hidrogen
membentuk pasangan A = T dan S = G
DNA
• Dua untai polinukleotida pada DNA m’btk
konformasi double heliks → arah untai yg
satu dg lainnya antiparalel.
• Pasangan basa berikatan : ikatan hidrogen
• Faktor yg menentukan konformasi DNA :
muatan negatif gugus fosfat dan afinitas ik.
Basa Purin & Pirimidin.
• Kedua untai polinukleotida m’btk belitan
searah jarum jam kekanan mengelilingi
sumbu tengah.
• Satu belitan : 10 ps nukleotida : jaraknya 3,4
A
Struktur memberikan kemudahan u/
m’hasilkan variasi2 gen yang berbeda
Struktur tdk random : urutan pasangan
basa dipelihara : PURIN – PIRIMIDIN
Panjang total DNA manusia dalam satu
set kromosom haploid : 3000 jt ps basa
Jk 1 Kilobasa ~ 1000 ps basa jadi
panjang DNA ~ 1,74 meter
Kromosom eukariot mengandung
sekuens DNA yang diulang beberapa kali
⇒ DNA Repetitive
 Komposisi kimia DNA memenuhi 2 syarat:

1. Fungsi Genotip atau Replikasi

Materi genetik mampu menyimpan informasi genetik &
mentransmisikan informasi tsb scr tepat dari parental
ke progeni dari generasi ke generasi.

2. Fungsi Fenotip - Ekspresi Gen

Materi genetik mengontrol perkembangan fenotip dari
organisme atau materi genetik mendikte pertumbuhan
& diferensiasi organ dari sel tunggal (zygot) sampai
organisme dewasa.
Materi genetik selain mengekspresikan dirinya scr
akurat jg mengontrol aktivitas setiap gen di tempat dan
waktu yang tepat. Co: sistem saraf disusun o/ sel2
saraf
• Ke-2 untai polinukleotida dpt dipisahkan ⇒
memutus ikatan hidrogen antara basa2 yg
berkomplentasi ⇒ Denaturasi : pemanasan 90°
C, diberi alkali (5M NaOH)
• Renaturasi/reannealing >< denaturasi
 DNA in EUKARYOTES is
packaged into chromosomes
http://www.paternityexperts.com/images/DNA-of-life.jpg

Humans have approximately 3

billion base pairs (1 m long)
60,000 to 100,000 genes

If the diameter of the DNA (2 nanometers) was as wide as a fishing

line (0.5 millimeters) it might stretch as far as 21.2 km (or 13.6 miles)
in length which would all have to be packed into a nucleus, the
equivalent size of 25 cm in diameter.
That is some packaging!
Chromosome Structure of Eukaryotes
© Pearson Education Inc, publishing as Pearson Prentice Hall. All rights reserved
Chromosome Nucleosome

DNA
double
helix
Coils

Supercoils

DNA is: Histones

in multiple
______________
chromosome bundles
______________
Found in __________
nucleus
Chromosome Structure of Eukaryotes
© Pearson Education Inc, publishing as Pearson Prentice Hall. All rights reserved

Eukaryotic DNA

chromosomes are Nucleosome double

made of
helix

DNA
_____ PROTEINS
& __________
called ___________
HISTONES

Together the DNA

Histones

& histone proteins forms a bead-like

NUCLEOSOME
structure called a ______________
 © Pearson Education Inc, publishing as Pearson Prentice Hall. All rights reserved

Chromosome Structure of Eukaryotes

Nucleosome
Chromosome

DNA
double
helix
Coils

Supercoils

Histones

Nucleosomes pack together to form thick

coiled fibers. When cell is NOT dividing,
these fibers are spread out in nucleus as
CHROMATIN (Allows reading of code)
___________.
Chromosome Structure of Eukaryotes
© Pearson Education Inc, publishing as Pearson Prentice Hall. All rights reserved
Chromosome Nucleosome

DNA
double
helix
Coils

Supercoils

When cell gets ready to divide, the

Histones

fibers pack even more tightly to form

chromosomes
___________.(Makes it easier to move
DNA during mitosis)
Image from: http://evolution.berkeley.edu/evosite/evo101/images/dna_bases.gif

HOW IS DNA COPIED?

The structure of DNA
explains how it can be
copied.

Each strand has all the info

needed to construct
matching
the __________other half.

If strands are separated,

_____________
base-pairing rules allow
you to fill in the
complementary bases.
 Replikasi DNA
• Peristiwa sintesis DNA
• Dapat terjadi dengan adanya sintesis rantai
nukleotida baru dari rantai nukleotida lama
• Prosesnya dengan menggunakan
komplementasi pasangan basa untuk
menghasilkan suatu molekul DNA baru yang
sama dengan molekul DNA lama
• The replication of DNA begins at one or more
sites on the DNA molecule where there is a
specific sequence of nucleotides called a
replication origin
 REPLIKASI DNA

Replikasi bersifat semi-konservative

Komponen aparatus replikasi:
1. DNA polimerase (4) : α, β, δ lokasi di
nukleus;γ pada mitokondria. Replikasi DNA
kromosom δ & α .
2. Helicase : u/ membuka heliks ganda
3. Faktor2 replikasi seperti : RF-A, RF-B, RF-C
4. Protein PCNA (Proliferating Cell Nuclear
Antigen) merupakan kofaktor Polimerase δ u/
menaikan kecepatan replikasi.
5. Protein2 lain (blm jelas diket)
 Figure 12–11 DNA Replication
Section 12-2

Original
strand DNA
New strand polymerase

Growth
DNA
polymerase
Growth

Replication Replication Nitrogenous

fork fork bases

New strand Original

Sites where strand separation and

strand

replication forks
replication occur are called _____________
 PROSES REPLIKASI

1. Pembukaan belitan DNA dg

E.helikase → replication fork
2. DNA untai tunggal → template u/
DNA baru
3. Arah sintesis DNA selalu dari 5’ ke
3’
Okazaki fragments,
are about 100 to 200 nucleotides long in eukaryotes
and 1000 to 2000 nucleotides long in prokaryotes
•RNA

Merupakan molekul genetik yang dimiliki

oleh virus
Berbentuk pita tunggal (Single stranded)
Merupakan polimer nukleotida yang terdiri
atas :
Gula ribosa
Basa pirimidin : sitosin (S)
urasil (U)
•RNA

• Mrpk suatu molekul polimer yg besar,panjang &

tidak bercabang → td 4 macam nukleotida yg
saling berikatan dg ikatan 3’-5’ fosfodiester

• Jenis RNA tergantung lokasi ditemukannya :

– Di nukleus : m RNA/RNA duta
– Di sitoplasma : t RNA/RNA pemindah
– Di ribosom : r RNA
 RIBONUCLEIC ACID (RNA)

• Fungsi :

– m RNA : menerima informasi genetik dari DNA →

“proses transkripsi”, berlangsung dalam nukleus
– t RNA : mengikat Asam amino yang terdapat dalam
sitoplasma. t RNA membawa asam amino yang telah
diikat di ribosom. Pada saat ini terjadi perubahan
informasi genetik yang dinyatakan oleh urutan basa
dari m RNA ke urutan AA dalam protein → “proses
translasi”
– r RNA : mensintesa protein, hasil akhir berupa
polipeptida
 SINTESA PROTEIN
• Ekspressi gen merupakan proses dimana
informasi yang dikode di dalam gen
diterjemahkan menjadi urutan asam amino
selama proses sintesa protein
• Proses sintesa protein terdiri menjadi
transkripsi dan translasi
 TRANSKRIPSI
• Sintesa RNA dari salah satu rantai DNA,
yaitu rantai cetakan/sense, sedangkan
rantai komplemennya adalah rantai
antisense
• Transkripsi terdiri menjadi 3 peristiwa yaitu
inisiasi (permulaan), elongasi
(pemanjangan) dan terminasi
(pengakhiran) rantai mRNA
Transcription: Eukaryote
• DNA sequence (message for protein) is
transcribed by mRNA
• Only one strand (non-coding strand) is
needed as a template
• Steps:

1. RNA polymerase splits H bonds in DNA

section
2. RNA polymerase travels along non-coding
strand of DNA. RNA nucleotides join in a
complimentary pattern (A=U, C=G)
3. A termination signal is reached,
transcription is over
4. mRNA strip detaches from DNA, DNA
helix closes up
5. mRNA is processed: Introns are cut out,
Exons are glued together, cap and tail are
added.
6. Mature mRNA leaves nucleus through
pores  cytoplasm for next step
RNA’s require EDITING before use

Image by Riedell
 TRANSLASI
• Sel menginterpretasikan suatu pesan
genetik dan membentuk protein yang
sesuai
• Pesan berupa serangkaian kodon di
sepanjang kodon mRNA, interpreternya
adalah tRNA
Transfer RNA
• Tahapan
translasi :
– Aktivasi →Proses aktivasi asam amino yang
bebas, terjadi didalam sitoplasma sel, oleh
karena ke-20 macam asam amino terdapat di
daerah ini. Proses mengaktifkan asam amino
dilakukan oleh enzim “aminoacyl-tRNA
synthetases” atau aminoacyl synyhetases”, yang
sifatnya spesifik untuk setiap macam asam
amino.
– Inisiasi →
– Elongasi →
– Terminasi → kodon nonsense : UAA,UAG, UGA
 INISIASI
initiation complex
: mRNA,
aminoacyl-tRNA,
ribosom
ELONGASI

pertumbuhan rantai
peptida
mjd protein lengkap
TERMINASI
Akhir proses sintesis
protein terjadi
Apabila terdapat 1 dari 3
kodon
penghenti yaitu UAA,
UAG, atau UGA.
Kodon tersebut tidak
dikenali oleh tRNA
Dan tidak mengkode
asam amino, namun
Merupakan sinyal untuk
ribosom menghentikan
proses translasi.
 PASCA TRANSLASI
• Perlu modifikasi agar terbentuk protein
fungsional.

• Contoh: Zimogen (inaktif)→melepas bbrp

komponen mjd aktif : tripsinogen →tripsin;
pepsinogen → pepsin
DOGMA SENTRAL
DNA polimerase

DNA REPLIKASI

RNA polimerase TRANSKRIPSI

RNA

TRANSLASI

PROTEIN
 KODE GENETIK
• Protein berupa gabungan banyak AA yang
membentuk polipeptida
• Jumlah AA : 20 macam sedang DNA hanya
t.d 4 basa (A,T,S,G) tetapi kemungkinan
terbentuknya varietas protein tidak terbatas
→?
• Nurenberg dkk (1968) : menciptakan kode
genetik sehingga mampu menerangkan
bagaimana sebuah gen mengontrol
pengaturan AA dalam protein tertentu
51
 KODE GENETIK
• Adalah suatu cara untuk menetapkan jumlah
serta urutan nukleotida yang berperan
menentukan posisi yang tepat dari AA dalam
rantai polipeptida yang bertambah panjang
• Tersusun atas triplet nukleotida : kodon.
Kombinasi AA yang mungkin terbentuk dari
4 buah basa : 43 = 64
• Bersifat universal
• Pengaturan kodon dalam RNA menentukan
struktur dan fungsi protein