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What is the “Central Dogma”?

•  It is the process by which the instructions in
DNA are converted into a functional product.

•  It was first proposed in 1958 by Francis Crick,

Chapter 3 discoverer of the structure of DNA.

Central
Dogma of
•  The central dogma (CD) of molecular biology
explains the flow of genetic information, from

Molecular Biology
DNA to RNA, to make a functional product, a
protein.

•  The CD suggests that DNA contains the
information needed to make proteins, and that
RNA is a messenger that carries this information
to the ribosomes.
•  The ribosomes serve as factories in the cell
where the information is ‘translated’ from a code
into the functional product.
•  The process by which the DNA instructions are
converted into the functional product is called
gene expression.
•  Gene expression has two key stages -
transcription and translation.
•  In transcription, the information in the DNA of
every cell is converted into small, portable RNA
messages.
•  During translation, these messages travel from
where the DNA is in the cell nucleus to the
ribosomes where they are ‘read’ to make specific
proteins.

The central dogma states that the pattern of

information that occurs most frequently in our
cells is:

①  From existing DNA to make new DNA (DNA

replication)
②  From DNA to make new RNA (transcription)
③  From RNA to make new proteins (translation).

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DNA Replication •  The two resulting double strands are identical (if
•  a.k.a. DNA synthesis, is the process of copying a
double-stranded DNA strand in a cell, prior to
cell division.
•  In eukaryotes, this is during !
the S phase of the cell cycle, !
preceding mitosis !
and meiosis.
the replication went well), and each of them
consists of one original and one newly-
synthesized strand (semi-conservative replication).
•  The process of replication consists of three steps,
initiation, elongation and termination.
•  Artificial DNA replication is carried out through
polymerase chain reaction.

DNA Replication - Steps

Initiation
•  In this step, several key factors are recruited to
an origin of replication.

•  This origin of replication is unwound, and the

partially unwound strands form a "replication
bubble", with one replication fork on either end.

The pre-replication complex consists of:

•  Each group of enzymes at the replication fork
moves away from the origin, unwinding and
replicating the original DNA strands as they
proceed.
•  Primers mark the individual sequences and their
start and end points, to be replicated.
•  The factors involved are collectively called the
pre-replication complex.
•  A topoisomerase, which introduces negative
supercoils into the DNA in order to minimize
torsional strain induced by the unwinding of the
DNA by helicase. This prevents the DNA from
knotting up.
•  A helicase, which unwinds and splits the DNA
ahead of the fork.
•  Single-strand binding proteins (SSB) swiftly
bind to the separated DNA, thus preventing the
strands from reuniting.

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•  A primase, which generates an RNA primer to
be used in DNA replication.
•  A DNA holoenzyme, which in reality is a
complex of enzymes that together perform the
actual replication.
•  The DNA polymerase can only travel on one
side of the original strand without any
interruption.
•  This original strand, which goes from 3’ to 5’, is
called the leading strand.
•  The complement of the leading strand, from 5’ to
3’, is the lagging strand.
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Elongation
•  After the helicase unwinds the DNA, RNA
primase is bound to the starting DNA site.
•  At the beginning of replication, an enzyme
called DNA polymerase binds to the RNA
primase, which indicates the starting point for
the replication.
•  DNA polymerase can only synthesize new DNA
from the 5’ to 3’ (of the new DNA).
•  Each time the helicase unwinds additional DNA,
new DNA polymerase needs to be added to the
5' to 3' strand to replicate against the direction of
DNA polymerase's action.
•  As a result, the DNA of the lagging strand is
replicated in a piecemeal fashion.
•  Another enzyme, DNA ligase, is used to connect
the so-called Okazaki fragments.
Termination
•  Termination occurs when DNA replication forks
meet one another or run to the end of a linear
DNA molecule.
•  Also, termination may occur when a replication
fork is deliberately stopped by a special protein,
called a replication terminator protein, that
binds to specific sites on a DNA molecule
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•  When the polymerase reaches the end of a •  To solve this problem, the ends of most
length of DNA, there is a potential problem due chromosomes consist of noncoding DNA that
to the antiparallel structure of DNA. contains repeat sequences.

•  Because an RNA primer must be regularly laid •  The end of a linear chromosome is called the
down on the lagging strand, the last section of telomere.
the lagging-strand cannot be replicated because
there is no DNA template for the primer to be
synthesized on.

•  The repeat DNA in the telomere is not essential •  Before the DNA replication is finally complete,
for survival, because it does not contain genes, enzymes are used to proofread the sequences to
so cells can endure the shortening of the make sure the nucleotides are paired up
chromosome at the telomere. correctly in a process called DNA repair.

•  Many cells use an enzyme called telomerase that •  If mistake or damage occurs, enzymes such as a
adds the repeat units to the end of the nuclease will remove the incorrect DNA. DNA
chromosome so the ends do not become too polymerase will then fill in the gap.
short after multiple rounds of DNA replication.

DNA Replication DNA Replication

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DNA Replication DNA Replication

Transcription Transcription : General Steps

①  RNA polymerase, together with one or more
•  It is the first of several steps of DNA based gene general transcription factors, binds to promoter
DNA.
expression, in which a particular segment of
DNA is copied into RNA (mRNA) by the
②  RNA polymerase creates a transcription bubble,
enzyme RNA polymerase. which separates the !
two strands of the !
•  During transcription, a DNA sequence is read by DNA helix. !
This is done by !
an RNA polymerase, which produces a breaking the !
complementary, antiparallel RNA strand called a hydrogen bonds !
primary transcript. between !
complementary !
DNA nucleotides.

③  RNA polymerase adds RNA nucleotides (which ⑥  If the cell has a nucleus, the RNA may be
are complementary to the nucleotides of one further processed. This may include
DNA strand). polyadenylation, capping and splicing.

④  RNA sugar-phosphate backbone forms with Polyadenylation

assistance from RNA polymerase to form an
RNA strand.
⑤  Hydrogen bonds of the RNA–DNA helix break,
freeing the newly synthesized RNA strand.
o  addition of poly(A) tail to an mRNA
o  The poly(A) tail protects the mRNA molecule
from enzymatic degradation in the cytoplasm
and aids in transcription termination, export of
the mRNA from the nucleus and translation.

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mRNA Capping
o  the 5’ cap is a specially altered nucleotide on the
5’ end of some primary transcripts such as
precursor mRNA

o  This process is highly regulated and vital in the

creation of stable and mature mRNA able to
undergo translation during protein synthesis.

Polyadenylation and Capping RNA Splicing

o  A form of RNA processing in which a newly
made precursor messenger RNA (pre-mRNA)
transcript is transformed into a mature mRNA.

o  During splicing, introns (Non-coding regions)

are removed and exons (Coding Regions) are
joined together.

RNA Splicing

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•  The stretch of DNA transcribed into an RNA Major Steps in Transcription

molecule is called a transcription unit and
encodes at least one gene.
•  If the gene encodes a protein, the transcription
produces messenger RNA (mRNA); the mRNA,
in turn, serves as a template for the protein's
synthesis through translation.
Initiation
•  It is the beginning of transcription.
•  It occurs when the enzyme RNA polymerase binds
to a region of a gene called the promoter.

•  This signals the DNA to unwind so the enzyme can

‘‘read’’ the bases in one of the DNA strands.

•  The enzyme is now ready to make a strand of

mRNA with a complementary sequence of bases.

Elongation Termination
•  Elongation is the addition of nucleotides to the
•  It is the ending of transcription, and occurs
mRNA strand.
when RNA polymerase crosses a stop
(termination) sequence in the gene.
•  RNA polymerase reads the unwound DNA strand
and builds the mRNA molecule, using
complementary base pairs. •  The mRNA strand is complete, and it detaches
from DNA
•  There is a brief time during this process when the
newly formed RNA is bound to the unwound DNA.

•  During this process, an adenine (A) in the DNA

binds to an uracil (U) in the RNA.

Initiation Transcription

Elongation

Termination

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Translation •  The polypeptide later folds into an active protein

•  It is the process in which ribosomes in the
cytoplasm or ER synthesize proteins after the
process of transcription of DNA to RNA in the
cell's nucleus.
and performs its functions in the cell.
•  The ribosome facilitates decoding by inducing
the binding of complementary tRNA anticodon
sequences to mRNA codons.

•  In translation, mRNA is decoded in the ribosome •  The tRNAs carry specific amino acids that are
decoding center to produce a specific amino acid chained together into a polypeptide as the
chain, or polypeptide. mRNA passes through and is read by the
ribosome.

Phases of Translation Elongation

Initiation •  The tRNA transfers an
amino acid to the tRNA
•  T h e ribosome corresponding to the next
assembles around codon.
the target mRNA.
•  The ribosome then moves
•  The first tRNA is (translocates) to the next
attached at the start mRNA codon to continue
the process, creating an
codon.
amino acid chain.

Termination
•  When a peptidyl tRNA encounters a stop codon,
then the ribosome folds the polypeptide into its
final structure

•  Termination happens when a stop codon (UAG,

UGA, UAA) in the mRNA enters the A site.

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Translation