You are on page 1of 48

Basic Molecular Genetics

Dr. Upik A. Miskad, PhD


Unhas Research Center

Medical genetics in the past :


Minor subject in the school.
Related to uncommon diseases.
Only specialist and affected patients
concern to the subject.
Medical genetics today :
Explain underlying molecular
pathobiology of many diseases.
Mainstream of medical science and
public health.
Powerful tool to establish: diagnosis,
classification, prognosis, prediction of
complication, as well as response to
the treatment.
Never ending story subject.

Dr. Upik A. Miskad, PhD


Unhas Research Center

CELLS

Cells are the basic units of living organisms.


Although a nerve cell looks entirely different
from a red blood cell, their organizations are
essentially the same.
Cells (Prokariotik dan eukaryotik)

Eukaryote versus prokaryote

Circular shape of microbial DNA

Cells

* building block of all life


* very small : - membrane
- cytoplasm : RNA
- nucleus
chromosomes
DNA

An organism may contain

many types of somatic


cells, each with distinct
shape and function.
However, they all have

the same genome.

The genes in a genome

Central Dogma

Gene

do not have any effect on


Genomeuntil
cellular functions
they are "expressed".
Transcription

RNA

Transcriptome

Different types of cells

express different sets of


genes, thereby exhibiting
Translation
various
shapes and
functions.

Protein

Proteome

The information goes only one way


The central dogma states
that once information
has passed into protein it
cannot get out again.
The transfer of information
.
from nucleic acid to nucleic
acid, or from nucleic acid to
protein, may be possible,
but transfer from protein to
protein, or from protein to
nucleic acid, is impossible.

GENE

By definition, a gene includes the entire nucleic acid sequence


necessary for the expression of its product (peptide or RNA).
Such sequence may be divided into regulatory region and
transcriptional region.

ASAM NUKLEAT
Asam Deoksiribonukleat
DNA (Deoxyribonucleid Acid)
Asam Ribonukleat
RNA (Ribonucleid Acid)

DNA
DNA adalah suatu

polimer yang panjang


tidak bercabang,
mengandung 2 rantai
polynucleotida yang
tersusun sebagai suatu
bentuk antiparalel yang
mengelilingi aksis.

DNA
DNA tersusun sebagai

suatu right-handed
double helix dengan
kelompokan gula-posfat
sebagai tulang
punggungnya dan basa
basa tersusun dibagian
pinggirnya

Nucleotides:
A - T
G - C

Sugar:
De oxy ribose
Ribose

Phosphate:

DNA
* can be renatured and denatured
* denatured : boils temperature
extreme of PH (PH < 3
PH > 10)
* renatured : 650 C

BASES
There are five different bases, each is denoted

by a single letter as given in the parenthesis:


Adenine (A), Cytosine (C), Guanine (G),
Thymine (T), and Uracil (U).
Among them,
A, C, G and T exist in DNA;
A, C, G and U exist in RNA.

Setiap nucleotida disusun oleh 3 komponen:


1. Gula/ pentose,
2. Basa/ base
3. Phosphate group.
Nucleosida
Disusun oleh gula/ pentosa dan basa saja

Basa berikatan dengan dengan Deoxyribosa


dengan Glycocyl linkage membentuk
NUCLEOSIDA.
Gugus gula pada ikatan basa dan gula bila
mengalami phosphorilasi akan mementuk
NUCLEOTIDA.

Phosphodiester bridge

Nucleotida dihubungkan

satu sama lain oleh


jembatan
phosphodiester
(Phosphodiester bridge)
Yang menghubungkan

antara gula pada


nucleotida yang satu
dengan phosphat pada
nucleotida yang lainnya

STRUKTUR KIMIA GULA/ PENTOSA

The chemical structure of pentose which contains five carbon


atoms, labeled as C1' to C5'.
The pentose is called ribose in RNA and deoxyribose in DNA,
because the DNA's pentose lacks an oxygen atom at C2'.

PENTOSA/GULA
RNA : RiboNucleid Acid

DNA: DeoxyriboNucleid Acid

Ada 2 macam Basa pada Asam nukleat:


Purin
Pirimidin
Purin: Struktur kimianya terdiri dari 2
cincin yang bergandengan
Terdiri dari 2 macam:

BASA

A: Adenine
G: Guanine

Pirimidin: Struktur kimianya terdiri


hanya 1 cincin.
Terdiri dari 3 macam:
C: Cystosine
T: Thymine
U: Urasil

STRUKTUR KIMIA
BASA
Ada 2 macam Basa pada
Asam nukleat:
1. Purin
2. Pyrimidin
Purin:
A: Adenine
G: Guanine
Pirimidin:
C: Cystosine
T: Thymine
U: Urasil

Computer model of base


pairing in DNA.
In a normal DNA molecule,
Adenine (A) is paired
with Thymine (T),
Guanine (G) is paired
with Cytosine (C).
The uracil (U) of RNA can
also pair with adenine (A),
since U differs from T by
only a methyl group located
on the other side of
hydrogen bonding.

FUNGSI BASA DALAM


DNA
Mempertahankan kestabilan DNA

dengan adanya ikatan hidrogen


antara pasangan pasangan basa
dari 2 rantai polinucleotida dalam
arah horisontal.

A DNA molecule has two strands,

held together by the hydrogen


bonding between their bases. As
shown in the figure:
Adenine can form two hydrogen
bonds with Thymine;
Cytosine can form three
hydrogen bonds with Guanine.

DNA Double Helix

The two strands form a "double

helix" structure, which was first


discovered by
James D. Watson and Francis Cri
ck
in 1953.
In this structure, also known as
the B form, the helix makes a
turn every 3.4 nm, and the
distance between two
neighboring base pairs is 0.34
nm. Hence, there are about 10
pairs per turn. The intertwined
strands make two grooves of
different widths, referred to as
the major groove and the
minor groove, which may
facilitate binding with specific
The normal right-handed "double helix"
proteins.
structure of DNA,
also known as the B form.

RNA (RIBONUCLEID ACID)

Ribonucleid Acid mempunyai struktur


kimia yang mirip DNA, kecuali:

1. Gulanya ribosa
2. Basa thymine (T) diganti dengan
Uracyl (U)
3. merupakan single strand (rantai
tunggal

RNA (RIBONUCLEID ACID)

Most cellular RNA


molecules are single
stranded.

They may form


secondary structures
such as stem-loop
and hairpin.

Ada 3 macam molekul


RNA
1. Messenger RNA (mRNA) RNA yang
mengarahkan pembentukan molekul
protein.
2. Transfer RNA (tRNA) RNA yang berfungsi
membawa Asam Amino ketempat
pembentukan protein.
3. Ribosomal RNA (rRNA) RNA yang berfungsi
membentuk komponen ribosom.

RNA (RIBONUCLEID ACID)

Molekul RNA disintesa dari DNA


melalui proses yang disebut DNA
Transcription.

Molekul RNA relative lebih pendek


dibandingkan dengan DNA karena
RNA dicopy dari satu daerah yang
terbatas.

Molekul RNA disintesa

dari DNA melalui


proses yang disebut
DNA Transcription.
mRNA membawa
informasi untuk sintesa
protein
Perhatikan tidak ada T
pada RNA, T (thymin)
diganti dengan U
(Urasil)

CENTRAL DOGMA
Essential steps involved
in the expression of
protein genes

The central dogma


According to the process,
the flow of genetic information is in the
following direction:

DNA > RNA > Protein.

GENE EXPRESSION

Gene expression" means the production of a protein or a functional


RNA from its gene.
Several steps are required:

Transcription: A DNA strand is used as the template to


synthesize a RNA strand, which is called the primary
transcript.
RNA processing: This step involves modifications of the
primary transcript to generate a mature mRNA (for protein
genes) or a functional tRNA or rRNA.
For RNA genes (tRNA and rRNA), the expression is complete
after a functional tRNA or rRNA is generated. However, protein
genes require additional steps:
Nuclear transport: mRNA has to be transported from the
nucleus to the cytoplasm for protein synthesis.
Protein synthesis: In the cytoplasm, mRNA binds to
ribosomes, which can synthesize a polypeptide based on the
sequence of mRNA.

PROSES TRANSKRIPSI
1. Pengkopian seluruh panjang DNA yang diinginkan
DNA
untuk dikopi Meliputi ekson dan intron dengan
bantuan enzym RNA polymerase membentuk
primary transkript

PROSES TRANSKRIPSI
2. Sebelum molekul RNA meninggalkan nukleus,
DNA
enzym pembentuk Komplex RNA (Complex of RNA

processing enzyme) akan menghilangkanSemua intron

PROSES TRANSKRIPSI
3. Setelah proses Splicing, RNA yang lebih pendek akan
DNA
Bergerak ke sitoplasma, untuk selanjutnya membentuk
Asam asam amino.

Exon : regio pada RNA yang mempunyai


kemampuan mengkode protein
Intron : regio pada RNA yang tidak mempunyai
kemampuan menkode Protein

Tiga nucleotida berturut turut dalam mRNA


menkode satu asam amino atau stop signal untuk
sintesa protein.
Tiga rangkaian nucleotida ini disebut CODON

CODON
Adalah suatu sequences yang terdiri dari 3
nukleotida yang mengkode satu asam
amino spesifik
Jadi seharusnya ada 43=64 asam amino
dari 4 kombinasi nukleotida yang ada.
Tapi yang hanya ditemukan dalam ptotein
adalah 20 asam amino
Jadi ada beberapa Codon membentuk
asam amino yang serupa.

CENTRAL DOGMA
Essential steps involved
in the expression of
protein genes

The central dogma


According to the process,
the flow of genetic information is in the
following direction:

DNA > RNA > Protein.

tRNA
Translasi dari mRNA ke protein
tergantung pada adaptor molekul
yang disebut tRNA.
tRNA Berfungsi mengenali dan
membawa asam amino yang akan
dibentuk.
Terdiri atas 80 nukleotida
Berbentuk seperti clover leaf

tRNA
Berbentuk tonjolan 3 dimensi.
Ada 2 daerah yang penting:

1. anticodon: daerah yang


disusun oleh 3 nukleotida yang
akan berikatan dengan kodon
komplemennya pada mRNA
2. amino acid attachment
region:
daerah pada tRNA yang akan
mengikat asam amino yang
dibawanya

PROSES TRANSLASI PROTEIN


Genetic code:
A process of translating of
the nucleotide sequence
into amino acid sequence
of protein.
During protein synthesis, the
ribosome binds to mRNA
and tRNA as shown in the
following figure.
Only the tRNA containing the
anticodon which matches
mRNA's codon may join
the complex

The mRNA-ribosome-tRNA complex

Pemesanan molekul
tRNA pada mRNA
memerlukan tempat
yang disebut RIBOSOME
RIBOSOME: adalah
suatu mesin
pembentukan protein
yang mengandung tRNA
yang akan membaca
informasi genetik pada

PROSES TRANSLASI PROTEIN

pada mRNA-ribosome-tRNA complex


Ribosome akan bergerak
sepanjang mRNA dan tRNA
yang ada didalamnya akan
membaca pesan genetik
sambil membawa asam
amino yang akan dirangkai
dengan asam amino yang
lain membentuk
polipeptida.

Polipeptida

PROTEIN
Protein dibentuk oleh rangkain polipeptida

dan polipeptida disusun oleh asam amino.


Asam asam amino dihubungkan satu sama
lain dengan ikatan peptida.

See you in the next lecture


Thank you

You might also like