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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 do not
have any effect on cellular
functions until they are
"expressed".

Different types of cells express


different sets of genes,
thereby exhibiting various
shapes and functions.
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


BASA
Ada 2 macam Basa pada Asam nukleat:
Purin
Pirimidin
Purin: Struktur kimianya terdiri dari 2 cincin yang
bergandengan
Terdiri dari 2 macam:
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
BASA YANG MEMBENTUK DNA
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 Crick 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
proteins.

The normal right-handed "double helix"


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.
mRNA
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 DNA
1. Pengkopian seluruh panjang DNA yang diinginkan
untuk dikopi Meliputi ekson dan intron dengan
bantuan enzym RNA polymerase membentuk
primary transkript
PROSES TRANSKRIPSI DNA
2. Sebelum molekul RNA meninggalkan nukleus,
enzym pembentuk Komplex RNA (Complex of RNA
processing enzyme) akan menghilangkanSemua intron
PROSES TRANSKRIPSI DNA
3. Setelah proses Splicing, RNA yang lebih pendek akan
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 mRNA
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