The document describes the central dogma of molecular biology, which states that DNA is replicated, then transcribed into RNA, and RNA is translated into protein. It provides details on DNA replication, transcription, and translation. DNA replication involves DNA polymerase copying DNA in the 5'-3' direction. Transcription involves RNA polymerase transcribing DNA into RNA. Translation occurs on ribosomes and involves mRNA being read in triplets to produce a polypeptide chain. The processes are generally conserved between prokaryotes and eukaryotes but have structural and mechanistic differences.

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