THE CENTRAL DOGMA OF MOLECULAR BIOLOGY

1. THE CENTRAL DOGMA OF
MOLECULAR BIOLOGY
by
Sadeeq Sheshe
Cancer Genetics Lab, Department of Bioscience,
COMSATS Institute of Information Technology, Islamabad

2.  The central dogma is a concept in molecular biology
that attempts to explains the key processes inside the
nucleus of the cell
 According to this concept, genetic information in DNA
is being replicated, later transcribed to RNA and then
translated into the protein
 It was earlier thought to be an irreversible process,
however the concept of reverse transcription proved
otherwise
Central Dogma

3.  DNA replication is the process of making new strands of
DNA using another DNA as a template
 DNA replication is catalyzed by the enzyme, DNA
polymerase whose structure is quite different in both
prokaryotic and Eukaryotic cells
 However, the process is semi-conservative in both
prokaryotic and eukaryotic organisms
 This means after the replication, each double stranded
DNA is made up of one original strand (template) and a
newly synthesized strand.
DNA Replication

4. Figure 1

5.  DNA replication occurs in 5’-3’ direction
 This means the hydroxyl (OH) on the 3’ on the
starting nucleotide attacks the alpha phosphate on
the incoming nucleotide thus establishing a phospho-
diester bond
 DNA replication does not start de novo but require
short strings of RNA oligos called primers
 Primers are synthesized by the enzyme primase
DNA replication

6.  DNA replication consists of 3 steps
 Initiation, Elongation and Termination
 Prokaryotic replication starts at an Origin of
replication
 These consensus sequences are recognised by the
different proteins involved in replication, forming the
pre-initiation complex
 The double strands unwinds and primers are
synthesized
Replication

7.  Certain proteins are assoicated with the replication
process
 Primase, Helicase, Topoisomerases and SSB proteins
 Primase synthesizes primers
 Helicase unwinds double stranded DNA
 Topoisomerases relieve tensional force generated due to
winding
 SSB holds single strands together preventing them to fold
and form helical structures
 Termination is achieved with the bi-directional synthesis
converging at a single point called TER
Replication

8. Figure 2

9.  This is the process of synthesizing an RNA molecule using
DNA as template
 It is an enzymatic process catalyzed by a DNA dependent
RNA polymerase
 RNA polymerase is also structurally different in both
prokaryotic and eukaryotic cells
 Also moves along5’-3’ direction but does not require
primer
 Question: why RNA polymerase does not require primer
and DNA polymerase do?
Transcription

10. Figure : promoter regions

11.  Just like the replication process, transcription also has 3 steps;
Initiation, Elongation and termination
 Transcription initiates by recognition of certain sequences on the
template Strand called promoter sequences. This are the start
point for transcription.
 This follows with the assembly of the transcription machinery
 And the elongation follows, in 5’-3’ direction, releasing
pyrophosphates
 The pyrophosphate is hydrolyzed to 2 inorganic phosphates with
release of energy
 This energy is the driving force for the process, just like in
REPLICATION
Transcription

12. Figure

13. Figure: Elongation

14.  The termination step is of two types
 The rho dependent and rho independent
 Rho is a protein that is part of the polymerase transcription
complex
 It searches for specific sequences and halt the polymease,
hence stopping the transcription
 While in rho independent termination, the transcriptional
machinery including the polymerase recognized certain
sequences along the template and stop
Transcription

15.  This is otherwise known as protein synthesis
 The information on the DNA that has been
transcribed into RNA is finally translated into a
protein
 The information on the RNA are recognized as codons
which are triplets of bases.
 Each amino acid has a codon although, one amino
acid can have more than one codon
 This is degeneracy of the protein code
Translation

16. Figure

17.  Translation takes place outside the nucleus, specifically on
the famous organelle, ribosome
 Although, the ribosome has two different structural
subunits in both prokaryotic and eukaryotic cells, it is quite
structurally distinct in both cells
 These sub units together with various proteins that assist
in translation form the translational machinery
 Each amino acids is first activated by attachment to an
Adapter RNA, tRNA catalysed aminoacyl-tRNA synthetases
Translation

18. Figure

19.  Translation also occurs sequentially in steps:
Initiation, elongation and termination
 Initiation factors help assemble the machinery and
allow the small subunits to search for the start codon,
AUG
 In prokaryotic cells, the Methionine for the starting
AUG is formylated to differentiate from other AUGs in
the subsequent parts of the sequence
 This distinction is far more complex in eukaryotic cells
Translation

20.  The process continues with the aminoacid-tRNA
entering the A site of the ribosome and the used
tRNA leaving via the E site
 The growing peptide keeps elongating in the P site of
the ribosome
 The termination is achieved by recognition of the stop
codons.
 There are 3 stop codons in all organisms
Translation

21.  After translation, the protein is premature
 It is modified were it becomes fully functional
 This include folding, cleavage, attachment of other
groups e.t.c
 This is the post translational modification of proteins
Translation

22.  Give at least 3 differences between replication and transcription
 Why is synthesis by both DNA and RNA polymerases occur in 5’-3’ direction?
Why not in 3’-5’ direction?
 What will happen if there is a mistake in replication?
 What is the difference between RNA transcript and its DNA template?
 What will happen if there is a mistake in translation?
 What is the difference between CODON and ANTICODON?
 Where does translation takes place? Why does it takes place in that place?
 How can you compare and contrast between the 3 process: translation,
transcription and replication?
 How can you differentiate between prokaryotic and Eukaryotic replication?
 Why is replication more complex in Eukaryotes than in prokaryotes?
Questions