ASAM NUKLEAT

1.Struktur dan Sifat DNA dan

RNA
2.Sistem Informasi Genetik

Pengantar

Bahan Genetik (DNA)

REPLIKASI
TRANSKRIPSI
TRANSLASI

Metabolisme

Protein
Struktural
Regulator

Replikasi DNA

Biokatalis
(enzim)

Replikasi RNA

Transkripsi

RNA

DNA

Transla
si

Transkripsi balik
(Reverse transcription)

Dogma Biologi Modern

(Central Dogma)

PROTEIN

Asam Nukleat

Asam nukleat adalah polimer nukleotida

Nukleotida sebagai monomer asam nukleat
Nukleotida terdiri dari gula, gugus
fosfat, dan basa nitrogen
Gula dan fosfat membentuk tulang
punggung asam nukleat

Peran Nukleotida

Penyusun asam nukleat (DNA & RNA)

Analog dengan peranan asam amino pd
protein
Pembawa energi dalam metabolisme seluler
(ATP: adenosine triphosphate)
Intermediet
komunikasi
sel
(cAMP:
adenosine
3,5-cyclic
monophosphate,
ppGpp: guanosine tetraphosphate)
Komponen struktural kofaktor enzim (NAD:
nicotinamide adenine dinucleotide, FAD:
Flavin adenin dinucleotide)

Karakteristik Pentosa dan Basa Nitrogen

Nukleotida

Basa Purin dan Pirimidin

Big word, small ring

Small word, big ring

Ingat: Penomoran dan struktur

umum cincin

eoksiribonukleotida (DNA)

ibonukleotida (RNA)

Ikatan Fosfodiester
Menghubungkan Nukleotida

Ikatan fosfodiester, khususnya pada

RNA, dapat dihidrolisis secara
nonenzimatik

Ikatan fosfodiester dalam polimer

Ikatan Fosfodiester
Menghubungkan
Nukleotida

9
RNA
cepat
terhidrolisis
dalam kondisi alkali, DNA
sulit terhidrolisis seperti
RNA; gugus 2-hidroksil pada
RNA
terlibat
langsung
dalam proses hidrolisis

Hidrolisis RNA dalam kondisi alkali

Notasi Asam Nukleat

A

C G

1
03

5
P

1
2
3

R
P

OH
5

pApTpCpGpApTpCpG-OH 3
5 pATCGATCG-OH 3

ATCGATCG
A short nucleic acid is referred to as an oligonucleotide. Short is somewhat
arbitrary, but polymers containing 50 or fewer.
A longer nucleic acid is called a polynucleotide.

Informasi Genetik
GEN

1
Sekuen DNA dengan panjang
1
minimum tertentu yang mengkode
urutan lengkap asam amino suatu
polipeptida, atau RNA
Arah transkripsi
ATG

PROMOTE
R

GEN
STRUKTURAL
Struktur dasar gen

STOP

TERMINAT
OR

Informasi Genetik
Bahan
Genetik Sel
Kromoso
m

Ekstrakromoso
m

Plasmid

DNA organel

Mitokondria

Kloroplas

1
2

Genomes and Genomics

The word genome, coined by German botanist

Hans Winkler in 1920, was derived simply by

combining gene and the final syllable of
chromosome.
If not specified, genome usually refers to the
nuclear genome!
An organisms genome is defined as the
complete haploid genetic complement of a typical
cell.
The genetic content of the organelles in the cell,
is not considered part of the nuclear genome.
In diploid organisms, sequence variations exist
between the two copies of each chromosome

Genetic Material in the Living Cells

o In a non-dividing cell the
nucleus is filled with a threadlike
material
known
as
"chromatin".
o Chromatin is made up of DNA
and proteins (mainly histones
and some non-histone acidic
proteins).
o Chromosome is a combination
of two words, i.e., Chromameans colour and Somesmeans body.

Chromosomes are the nucleoprotein

structures that carry the genetic
information. In eukaryotes they are
located in the cell nucleus.
" Genome" is all the DNA contained in
an organism or a cell, which includes
the chromosomes plus the DNA in
mitochondria
(and
DNA
in
the
chloroplasts of plant cells).

Chromosomes
The eukaryotic genome is made up of
DNA/protein
complexes
called
chromosomes.
Gene sequences embedded within
chromosomes must still be available
for transcription by RNA polymerases
and all of the DNA must be capable of
being copied by DNA polymerases.
Chromosomes
have
two
main
functions:
i. To ensure that the DNA is segregated
equally to daughter nuclei at cell
division, and to ensure that the
integrity of the genome is maintained
and accurately replicated in each cell

Each chromosome carries a couple of thousand genes.

Many of these are common to all human beings.
So, 99.9% of your DNA is identical to everyone else's.
The remaining 0.1% influences the differences between us.
height, hair color and susceptibility to a particular disease.
Environmental factors, such as lifestyle also influence the
way we look and our susceptibility to disease

Chromosome
number/size

There are mainly two type:

i. Somatic chromosome number (2n), it is the
number of chromosome found in somatic,
merismatic and tissues of species.
ii. Gametic chromosome (n), it is one half of the
somatic number basically it is the haploid number.
. Chromosome size shows variation depending
upon stage of cell division, it is from 1 to 30 in
length and diameter from 0.2
to 2 .
. Longest and thinnest chromosome seen during
interphase.

Types of chromosomes
There are four types of chromosomes based upon the
position of the centromere.
1) Metacentric: the centromere occurs in the centre and all the
four chromatids are of equal length.
2) Submetacentric: the centromere is a little away from the
centre and therefore chromatids of one side are slightly
longer than the other side.
3) Acrocentric: the centromere is located closer to one end of
chromatid therefore the chromatids on opposite side are very
long.
4)
Telocentric: the centromere is placed at one end of the
chromatid and hence only one arm. Such telocentric
chromosomes are not seen in human cells.

Prokaryotic and Eukaryotic Cells

Chromosomal differences
Prokaryotes
The genome of E.coli contains
amount of 4X106 base pairs
> 90% of DNA encode protein
Lacks
a
membrane-bound
nucleus.
Circular DNA and supercoiled
domain

Histones not present

Continue
o Prokaryotic genomes generally
contain one large circular piece
of DNA referred to as a
"chromosome" (not a true
chromosome in the eukaryotic
sense).
o Some bacteria have linear
"chromosomes".
o Many bacteria have small
circular DNA structures called
plasmids which can be
swapped between neighbors
and across bacterial species.

Plasmid
o The term plasmid was first
introduced by the American
molecular
biologist
Joshua
Lederberg in 1952.
o A plasmid is separate from,
and can replicate independently
of, the chromosomal DNA.
o Plasmid size varies from 1 to
over 1,000 (kbp).

Continue
Eukaryotes
The genome of yeast cells contains
1.35x107 base pairs
A small fraction of the total DNA
encodes protein.

Many repeats of non-coding

sequences

All chromosomes are contained in a

membrane bound nucleus

DNA is divided between two or more

chromosomes

A set of five histones

DNA packaging and gene expression

regulation

Eukaryotic Genome
Nuclear
Mitochondrial
Plasmids (in yeast and plant
chloroplasts)

Number of genes in the human

genome
Number of genes at least 100,000.
HOWEVER, the number of proteinencoding genes
is only ~20,000 to 25,000.

How can we explain this?

Lecture
no. 5

Mitochondrial DNA
Mitochondrial DNA is a single double stranded circular
molecule.
There are several copies in each mitochondrion and there
are many mitochondria in each of your cells.
Mitochondrial DNA is similar to prokaryotic DNA. There are
no histones or any other protein associated with mt DNA.
The genes contain no introns. Maternal inheritance.
Because it is in a highly oxidizing environment it has a
much higher rate of mutations than nuclear DNA.
The genes in mt DNA code for mitochondrial ribosomes
and transfer RNAs.
Some genes code for polypeptide subunits of the electron
transport chain common to all mitochondria.

DNA MOLECULES HAVE DISTINCTIVE BASE

COMPOSITIONS

21

A most important clue to the structure of DNA came from the

work of Erwin Chargaff and his colleagues in the late 1940s.
1. The base composition of DNA generally varies from one species to
another.
2. DNA specimens isolated from different tissues of the same species
have the same base composition.
3. The base composition of DNA in a given species does not change with
an organisms age, nutritional state, or changing environment.
4. In all cellular DNAs, regardless of the species, the number of
adenosine residues is equal to the number of thymidine residues
(that is, A = T), and the number of guanosine residues is equal to the
number of cytidine residues (G = C). From these relationships it
follows that the sum of the purine residues equals the sum of the
pyrimidine residues; that is, A + G = T + C.

Erwin Chargaf

DNA Is a Double Helix

22

Rosalind Franklin and Maurice Wilkins

used the powerful method of x-ray
diffraction (1950).
DNA molecules are helical with two
periodicities along their long axis, a
primary one of 3.4 and a secondary
one of 34 .

In 1953 Watson and Crick postulated a

three dimensional model of DNA
structure that accounted for all the
available data. Based on: X-ray data
and Chargaf rule.

DNA Structure
DNA consists of two helical
chains wound around the same
axis in a right-handed fashion
aligned in an antiparallel
fashion.
There are 10.5 base pairs, or
36 , per turn of the helix.
Alternating deoxyribose and
phosphate groups on the
backbone form the outside of
the helix.
The planar purine and
pyrimidine bases of both
strands are stacked inside the
helix.

23

Comparison of A, B, and Z forms of

DNA
A

29

Major
groove

Minor
groove

Favored
solutions
relatively
water

in
many
that
are
devoid of

Most stable
structure

Pyrimidines alternate with

purines, alternating C and G.
To form the left-handed helix
in
Z-DNA,
the
purine
residues flip to the syn

Comparison of A, B, and Z forms of DNA

30

Enzymes in DNA replication

Helicase unwinds
parental double
helix

Binding
proteins
stabilize
separate
strands

Exonuclease removes
DNA polymerase
binds nucleotides RNA primer and inserts
to form new strandsthe correct bases

47

Primase adds
short primer
to template
strand

Ligase joins
Okazaki
fragments and
seals
other nicks in

48

Replication

49
3
3

5
3
5

Helicase protein binds to DNA sequences called

origins and unwinds DNA strands.
Binding proteins prevent single strands from rewinding.
Primase protein makes a short segment of RNA
complementary to the DNA, a primer.

Replication

50

Overall direction
of replication

3
3

5
3
5

3
5

DNA polymerase enzyme adds DNA nucleotides

to the RNA primer.

Replication
Overall direction
of replication

51
3
3

5
3
5

Leading strand synthesis continues in a

5 to 3 direction.

3
5

Replication
Overall direction
of replication

52
3
3

5
Okazaki fragment

3
5

3 5

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication
Overall direction
of replication

53
3
3

5
Okazaki fragment

3
5

35

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication

54
3
5

3
5
3
5

3 5

35

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication

55
3
5

3
5
3
5

35

35

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication

56
3
5

3
5
3
5

35

35

3
5

Exonuclease enzymes remove RNA primers.

Replication

57
3

3
5
3
5

35

3
5

Exonuclease enzymes remove RNA primers.

Ligase forms bonds between sugar-phosphate
backbone.