DNA Replication

Siufui hendrawan
Biochemistry and Molecular Biology
Department
Faculty of Medicine
Tarumanagara University

DNA is the chemical basis of heredity

All truths are easy to understand once they are

discovered; the point is to discover them.
Galileo Galilei
Italian astronomer & physicist (1564 - 1642)

DNA contains genetic information

DNA is organized into chromosomes

One percent of cellular DNA is in mitochondria

Human Genome

The haploid genome of each human cell consists

of 3x109 base pairs of DNA, subdivided into 23
chromosomes.

Most of the mammalian genome is redundant and

much is not transcribed

Genes is the fundamental units of genetic

information

Coding regions are often interrupted by

interventing sequences

More than half the DNA in eukaryotic organisms is

in unique or nonrepetitive sequences

Allele

The Central Dogma

The Central Dogma describes the Flow of
Information from DNA RNA protein.

DNA Replication

Transcription

Translation

DNA provides a template for replication and

transcription
The genetic information stored in the DNA serves
two purpose
1. it is the source of information for synthesis of
allprotein molecules of the cell and organism
2. it provides the information inherited by daughter
cells or offspring

Template strand and coding strand

DNA synthesis occurs during the S phase of the

cell cycle

Chromosomal recombination is one way of

rearranging genetic material
Sister chromatids exchange

The Structure of DNA

DNA is a double-stranded helix with antiparallel
strands [Watson and Crick].

Double helix

Antiparallel

The Structure of DNA

DNA contains FOUR Deoxynucleotides,
The amounts of A = T, G = C, and purines =
pyrimidines [Chargaffs Rule].
Nucleotides in each strand are linked by 5-3
phosphodiester bonds
Bases on opposite strands are linked by hydrogen
bonding: A with T, and G with C.

Ribose has 2 OH, while Deoxyribose lacks 2 OH

Nucleoside -- nitrogenous
base & sugar
Nitrogenous base attaches
to 1 sugar Carbon

Nucleotide -- nitrogenous
base, sugar & phosphate
Phosphate attaches to 5
Carbon of sugar

DNA exist in supercoiled froms

DNA Replication
DNA Replication

DNA must replicate during each cell division

THREE alternative models for DNA replication
were hypothesized:
Semiconservative replication
Conservative replication
Dispersive replication

Meselson and
Stahls experiment
proved replication
of DNA to be
semiconservative

The Mechanism of DNA Replication

The origin of replication

Unwinding of DNA
Formation of the replication fork
Initiation and elongation of DNA synthesis

The Mechanism of DNA Replication

DNA replication is catalyzed by DNA polymerase
DNA polymerase needs an RNA primer
DNA polymerase adds nucleotides to the 3 end of
the growing strand
Nucleotides are added by complementary base
pairing with the template strand
The substrates, deoxyribonucleoside
triphosphates, are hydrolyzed as added, releasing
energy for DNA synthesis.

The Mechanism of DNA Replication

Many proteins assist in DNA replication
DNA helicases unwind the double helix, the
template strands are stabilized by other proteins
Single-stranded DNA binding proteins make the
template available

The Mechanism of DNA Replication

Many proteins assist in DNA replication

DNA helicases
Single-stranded DNA binding proteins
RNA primase catalyzes the synthesis of short RNA
primers, to which nucleotides are added.
DNA polymerase III extends the strand in the 5-to3 direction

The Mechanism of DNA Replication

DNA polymerase I degrades the RNA primer and
replaces it with DNA
DNA ligase joins the DNA fragments into a
continuous daughter strand

RNA primase

The Mechanism of DNA Replication

DNA synthesis on the leading strand is continuous
The lagging strand grows the same general
direction as the leading strand (in the same
direction as the Replication Fork). However, DNA
is made in the 5-to-3 direction
Therefore, DNA synthesis on the lagging strand is
discontinuous
DNA is added as short fragments (Okasaki
fragments) that are subsequently ligated together

The DNA polymerase complex

Chain elongation
Processivity
proofreading

DNA synthesis and replication are rigidly controlled

Pada Sickle cell anemia, terjadi mutasi Glu6 (rantai ) pada Hb A digantikan oleh Val6 pada HbS

DNA repair