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 Informasi genetik
• Disimpan dalam urutan basa sepanjang
rantai asam nukleat
• Dogma sentral :

→ RNA → Protein
Transkripsi Translasi
Replikasi

DNA
Ekspresi gen
Asam nukleat
Rantai DNA
Replikasi semikonservatif
 Replikasi DNA

Templat
Primer
DNA polimerase
Nukleotida (dATP, dGTP, dTTP, and dCTP)
Ion Mg2+
Arah 5’→3’
DNA Replication
 Let’s meet
the team…
DNA Replication
• Large team of enzymes coordinates replication
 Replication: 1st step
• Unwind DNA
– helicase enzyme
• unwinds part of DNA helix
• stabilized by single-stranded binding proteins
helicase

single-stranded binding proteins replication fork

 Replication: 2nd step
 Build daughter DNA
strand
 add new
complementary bases
 DNA polymerase III

But…
Where’s the
We’re missing
ENERGY
DNA something!
for the bonding!
Polymerase III What?
 Energy of Replication
Where does energy for bonding usually come from?
We come
with our own
energy!
You energy
remember energy
ATP!
Are
Are there
there
other
other ways
energy
to get energy
nucleotides?
out
You of
betit?
!

And we
leave behind a
ATP
GTP
CTP
TTP nucleotide! AMP
ADP
CMP
TMP
GMP
modified nucleotide
 Energy of Replication
• The nucleotides arrive as nucleosides
– DNA bases with P–P–P
• P-P-P = energy for bonding
– DNA bases arrive with their own energy source for
bonding
– bonded by enzyme: DNA polymerase III

ATP GTP TTP CTP

 5 3
Replication
energy
DNA
• Adding bases Polymerase III

– can only add energy

nucleotides to DNA
Polymerase III
3 end of a growing
DNA strand energy
DNA
• need a “starter”
Polymerase III
nucleotide to
bond to
energy
DNA
– strand only grows Polymerase III
53
B.Y.O. ENERGY!
The energy rules 3 5
the process
5 3 5 need “primer” bases to add on to 3

energy
no energy


to bond
energy
energy

energy
energy

ligase
energy

energy

3 5 3 5
 Okazaki

Leading & Lagging strands

Limits of DNA polymerase III
 can only build onto 3 end of an
existing DNA strand 5


f rag ments
ki
Okaza 5
3 5 5 3
3
5 Lagging strand
3
ligase
growing 3
replication fork
5
Leading strand

Lagging strand
3
5

3
 Okazaki fragments DNA polymerase III
 joined by ligase
Leading strand
 “spot welder” enzyme  continuous synthesis
Replication fork / Replication bubble
3 5

5 3

DNA polymerase III

leading strand
5
3 3 5
5 5
5 3 3
lagging strand

3 5
5
3 lagging strand leading strand
5 growing
3 replication fork 5
5 growing
replication fork 5
leading strand 3
lagging strand
3
5
5 5
Starting DNA synthesis: RNA primers
Limits of DNA polymerase III
 can only build onto 3 end of an
existing DNA strand 5

3 5 3
5
3
3 5

growing 3 primase
replication fork DNA polymerase III
5

RNA 5

RNA primer 3
 built by primase
 serves as starter sequence for DNA
polymerase III
 Replacing RNA primers with DNA
DNA polymerase I
 removes sections of RNA primer and
replaces with DNA nucleotides DNA polymerase I
5

3

3
5 ligase
growing 3
replication fork
5

RNA 5

3

But DNA polymerase I still

can only build onto 3 end of
an existing DNA strand
Chromosome erosion Houston, we
have a problem!

All DNA polymerases can

only add to 3 end of an DNA polymerase I
existing DNA strand 5

3

3
5
growing 3
replication fork DNA polymerase III
5

RNA 5

Loss of bases at 5 ends 3

in every replication
 chromosomes get shorter with each replication
 limit to number of cell divisions?
 Telomeres
Repeating, non-coding sequences at the end
of chromosomes = protective cap
 limit to ~50 cell divisions 5

3

3
5
growing 3 telomerase
replication fork
5

5
Telomerase
TTAAGGG TTAAGGG TTAAGGG 3
 enzyme extends telomeres
 can add DNA bases at 5 end
 different level of activity in different cells
 Replication fork
DNA
polymerase III lagging strand
DNA
polymerase I
3’
Okazaki primase
fragments 5’
5’ ligase
3’ 5’ SSB

3’ helicase

DNA
polymerase III
5’ leading strand
3’
direction of replication
SSB = single-stranded binding proteins
 DNA polymerases
• DNA polymerase III
– 1000 bases/second! Roger Kornberg
2006
– main DNA builder
• DNA polymerase I
– 20 bases/second
– editing, repair & primer removal
DNA polymerase III Arthur Kornberg
enzyme 1959
 Editing & proofreading DNA
• 1000 bases/second =
lots of typos!
• DNA polymerase I
– proofreads & corrects typos
– repairs mismatched bases
– removes abnormal bases
• repairs damage
throughout life
– reduces error rate from
1 in 10,000 to
1 in 100 million bases
 Fast & accurate!
• It takes E. coli <1 hour to copy
5 million base pairs in its single
chromosome
– divide to form 2 identical daughter cells
• Human cell copies its 6 billion bases &
divide into daughter cells in only few hours
– remarkably accurate
– only ~1 error per 100 million bases
– ~30 errors per cell cycle
DNA virus dari RNA
 Ekspresi gen
Transkripsi Translasi
DNA RNA Protein
Tipe RNA
RNA polimerase
Transkripsi
5' 3'
3' 5'
Konsensus promoter
 Transcription factors
• RNA-pol does not bind the promoter
directly.
• RNA-pol II associates with six
transcription factors, TFII A - TFII H.
• The trans-acting factors are the
proteins that recognize and bind
directly or indirectly cis-acting
elements and regulate its activity.
TF for eukaryotic transcription
Video MCB0402
mRNA eukariot
 The termination function of  factor

The  factor, a hexamer, is a ATPase

and a helicase.
• The nascent RNA, also known as
primary transcript, needs to be
modified to become functional
tRNAs, rRNAs, and mRNAs.
• The modification is critical to
eukaryotic systems.
 Capping at the 5- end
OH OH
O
N
NH
O O O
O 5'
H2N N N H2C O P O P O P O CH 2 N NH 2
N
5' O
O O O
HN
N
O
CH 3
O OH
Pi
O P O AAAAA-OH 3'
O

m7GpppGp----
• The capping process occurs in nuclei.

• The cap structure of mRNA will be

recognized by the cap-binding protein
required for translation.
• The capping occurs prior to the
splicing.
 Poly-A tailing at 3 - end
• There is no poly(dT) sequence on the
DNA template.  The tailing process
dose not depend on the template.
• The tailing process occurs prior to
the splicing.
• The tailing process takes place in the
nuclei.
mRNA splicing

mRNA

DNA

The matured mRNAs are much shorter than

the DNA templates.
Ekson dan intron
 Translasi
• Tiga nukleotida mengkode satu asam
amino
• Kode tidak tumpang tindih
• Kode tidak ada jeda
• Kode genetik, 61 triplet untuk kode asam
amino dan 3 untuk kode stop
Start dan stop sinyal
 Post-Translational Modification
• New polypeptides usually fold themselves spontaneously
into their active conformation. However, some proteins
are helped and guided in the folding process by
chaperone proteins
• Many proteins have sugars, phosphate groups, fatty
acids, and other molecules covalently attached to certain
amino acids. Most of this is done in the endoplasmic
reticulum.
• Many proteins are targeted to specific organelles within
the cell. Targeting is accomplished through “signal
sequences” on the polypeptide. In the case of proteins
that go into the endoplasmic reticulum, the signal
seqeunce is a group of amino acids at the N terminal of
the polypeptide, which are removed from the final protein
after translation.
 Protein synthesis
1. DNA unwinds
2. mRNA copy is made of one of the DNA strands.
3. mRNA copy moves out of nucleus into cytoplasm.
4. tRNA molecules are activated as their complementary amino acids are
attached to them.
5. mRNA copy attaches to the small subunit of the ribosomes in cytoplasm. 6
of the bases in the mRNA are exposed in the ribosome.
6. A tRNA bonds complementarily with the mRNA via its anticodon.
7. A second tRNA bonds with the next three bases of the mRNA, the amino
acid joins onto the amino acid of the first tRNA via a peptide bond.
8. The ribosome moves along. The first tRNA leaves the ribosome.
9. A third tRNA brings a third amino acid
10. Eventually a stop codon is reached on the mRNA. The newly synthesised
polypeptide leaves the ribosome.
Summary
Pengendalian ekspresi gen

Operon Jacob-Monod