Introduction Biology Molecular

Pendahuluan
Biologi Molekuler
DOGMA CENTRAL
DNA
RNA
Protein
Mathematical Biosciences Institute (Ohio State Univ), 2 October 2003
Dogma central Biologi Molekuler
DNA Sequence
(splited by
genes)
RNA
Asam
amino
Adapted from http://www.bioinfbook.org/
protein
fenotip
DNA
Gula
Fosfat
Basa (A,T, C or G)
• DNA adalah komponen yang tersusun dari
dari molekul-molekul yang disebut nukleotid
•Masing-masing nukleotid mengandung fosfat,
gula dan basa nitrogen.
• Ada empat basa: Adenine (A), Guanine (G),
Cytosine (C), and Thymine (T)
DNA: structure
• Ikatan gula-fosfat pada nukleotid
merupakan backbone dari ikatan pada
DNA
•Empat basa dari DNA dibentuk
sepanjang “backbone” disebut dengan
DNA sequence.
•Dua DNA saling berikatan di antara
pasangan basa
•Dua ikatan basa yang mungkin yaitu:
•A-T, C-G.
• Dua untai DNA mempunyai formasi
struktur double helixTwo.
Source of diagram: http://www.cs.utexas.edu/users/s2s/latest/dna1/src/page2.html
DNA: tersusun dalam kromosom

Each chromosome is essentially a
package for a very long, continuous DNA
double strand.
Lodish et al. Molecular Biology of the Cell (5th ed.). W.H. Freeman & Co., 2003.
DNA: di-splid oleh gen-gen
promoter
Exon 1
Intron 1
Exon 2
Intron 2
Exon 3
gene
• Gen merupakan bagian dari DNA yang membawa informasi
untuk membentuk protein.
• 2-3% dari DNA manusia adalah gen, gen yang tidak aktif (rest)
disebut junk DNA
•Promotor terlelak di bagian awal dari komponen gen. Promotor
aktif saat gen akan bekerja.
• Pada banyak gen euryotic, gen adalahsekuen DNA yang
mempunyai kode, yang juga disebut sebagai exon. Bagian yang
tidak membawa kode genetik disebut sebagai intron.
RNA
• RNA (ribonucleic acid) adalah
intermediet antara DNA dan protein.
• RNA merupakan single strand dari
asam nukleat.
• Basa nitrogen T (Thymine) pada
RNA terganti oleh U (Uracil)
• Tidak seperti DNA, yang terlokasi
di inti, RNA juga dapat ditemukan di
sitoplasma.
• Pada inti, kode gen
ditranskripsikan pada RNA.
Selanjutnya RNA akan keluar dari
inti ke nukleus dalam sitoplasma,
dimana RNA ditranslasi menjadi
asam amino.
Source of diagram: http://en.wikipedia.org/wiki/RNA
Another view of central dogma
Gen diekspresikan pada 3 step:
1) Transkripsi: Sintesis RNA
2) Splicing: penghilangan intron dari RNA
3) Translasi: Sintesis Protein
Transkripsi
• Transkripsi diinisiasi oleh kompleks dari
faktor=faktor transkripsi yang berikatan dengan
promotor.
•An enzyme, RNA polymerase II, travels along
the gradually unzipped DNA template and
polymerizes nucleotides into an RNA.
• The sequence of nucleotides on DNA template
determines the sequence on RNA by following
the rule of base-pair complementarity, i.e., A –
U, T- A, C – G, G – C.
• Transcription continues until entire gene is
copied to RNA.
Animation
Source of diagram: http://ghs.gresham.k12.or.us/science/ps/sci/ibbio/chem/nucleic
Splicing
pre mRNA
Exon 1
Intron 1
Exon 2
mature mRNA
Intron 2
Exon 3
Translation (1)
• By translation, the nucleotide
sequence on mRNA
determines the amino acid sequence
by genetic code.
• Genetic code: three base pairs of
RNA (called a codon) determine
one amino acid based on a fixed
table.
• Translation always starts at AUG
(start codon), and ends with any of
UAA, UAG, or UGA (stop codon)
Translation (2)

Transfer RNAs (tRNAs): small RNA
molecules. Most of the tRNAs
function as carriers of amino acids
and participate in protein synthesis.

For example, the tRNA with the
anticodon CGG corresponds with
the codon GCC and attaches
alanine amino acid onto the peptide
chain.

Ribosome: a complex of protein and
rRNA
Animation
Source of diagram: http://www.wiley.com/legacy/college/boyer/0470003790/structure/tRNA/
Summary

Central dogma of molecular biology

Three components
 DNA
 RNA
 Protein

Three steps
 transcription
 splicing
 translation
Cell – cell communication
Protooncogenes
encode
components
of growth
factor signal
transduction
pathways
Components
shown in yellow
are known protooncogenes
The VEGF family and its
receptors
VEGF-A
VEGF-B
PlGF
VEGF-A
VEGF
receptor-2
VEGF
receptor-1
P–
P–
–P
–P
VEGF-C
VEGF-D
VEGF
receptor-3
P–
P–
–P
–P
P–
P–
–P
–P
Migration, permeability, DNA synthesis, survival
Angiogenesis
Lymphangiogenesis
Adapted from Ferrara N. Nat Med 2003;9:669–76
VEGF signal transduction and
its effects
VEGF
 Permeability
VEGF-C
VEGF-D
VEGF
VEGF
receptor-1
VEGF
receptor-2
–P
–P
P–
P–
–P
–P
P–
P–
VEGF
receptor-3
P–
P–
Ca2+
PLC
PLC
Cation
channel
IP3
Calcium
release
DAG
DAG
–P
–P
PLC
P13K
Protein kinase C
Raf-1
MAPK
Proliferation, migration
 Permeability
SAPK/
JNK
Apoptosis
Survival
Protein kinase B
Proliferation
Migration
VEGF binding to VEGF receptor-2 activates a signalling cascade resulting in cellular effects
Shibuya M. Cell Struct Funct 2001;26:25–35
Agents targeting the
VEGF pathway
Antibodies inhibiting
VEGF receptors
Soluble VEGF receptors
(VEGF-TRAP)
Antibodies inhibiting VEGF
(e.g. bevacizumab)
 Permeability
VEGF
Cation
channel
VEGF
receptor-2
P–
P–
–P
–P
Small-molecules
inhibiting VEGF receptors
(TKIs)
(e.g. PTK-787)
P–
P–
–P
–P
P–
P–
Migration, permeability, DNA synthesis, survival
Ribozymes
(Angiozyme)
Angiogenesis
Lymphangiogenesis
–P
–P
Signal Transduction from Receptor to Nucleus
Via RAS p21
Growth factor
P
Ras
Ras
P
Grb2
GTP
GTP
GDP
Sos
P120-GAP
14-3-3
Neurofibromin
1 2
14-3-3
1
2
14-3-3
1
2
3
3
Active
Raf
3
MEK
P13-K
14-3-3
1
Rac and Rho
pathway
2
ERK1
ERK1
3
Inactive Raf
Transcription
factors etc.
Nucleus
Morphological
change
?
DNA
synthesis
Regulators : proliferation,
differentiation, apoptosis, repair


Genome :
Genes :






Cell cycle
Differentiatio
Apoptosis
Repair
Metabolism
etc
Transcriptome


Proteome
Protein:
RNA

RNA

RNA
RNA


RNA
RNA

cyclin, CDK,CDKI
GF : GM-CSF, FGF
Bcl-2, p53,
caspase
Gadd, enzym
repair
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