Central Dogma

DNA..............................................................................................................................2
Overview........................................................................................................................... 2
DNA Replication (8 steps)................................................................................................2
End replication problem..................................................................................................3
RNA Transcription......................................................................................................5
Protein............................................................................................................................... 6
DNA

Overview

- Double helix
- Right hand twisted ->
- Antiparallel
- Nitrogenous base:
 Purine: A, G
 Pyramidine: T, C
 A-T forms 2 H-bonds, C-G forms 3 H-Bonds
- Sugar phosphate backbone: 3’ joined to 5’ by phosphodiester bond (Hydroxyl
(OH) and Phosphate (PO4) are present for condensation reaction
- Replication is semi-conservative

DNA Replication (8 steps)

1. Helicase: Unwinds DNA (Breaks hydrogen bonds between base pairs)

2. Single stranded binding proteins: Stabilise DNA’s strands, prevent
annealing
3. Topoisomerase: Relieves strain by temporarily cutting phosphate backbone
of DNA strands. Can now swivel.
4. RNA Primase: Synthesize RNA primer. Polymerase unable to start without
primer.
5. DNA Polymerase III: Synthesizes complementary daughter strand (5’  3’).
Sliding clamp hold it in place.
6. RNase H: Removes primer
7. DNA Polymerase I: Replaces RNA of primer with DNA
8. Ligase: Joins Okazaki fragments together (catalyses formation of
phosphodiester bonds between 3’ -OH and 5’ phosphate of 2 fragments
DNA Replication Details

- Since DNA only replicated from 5’  3’ (DNA polymerase can only attach new
nucleotide to OH side and not phosphate side), Okazaki fragments form on
the lagging strand. RNA primer inserted at the start of every fragment.
- Leading/lagging strand refers to newly replicated strands

End replication problem

- DNA replication can only occur when there is a free

-OH group on the 3’ end to attach extend from.
- RNA primers provide this -OH group for DNA
polymerase to extend from.
- However, at the 3’ end of the lagging strand, there is
a part where the RNA primer attaches (Red
coloured).
- Once it is removed there will be a section where DNA
polymerase is unable to add on to as there is no -OH
group to extend from.
- Thus, a section is not replicated and each replication
results in a shorter and shorter DNA.

- Werner syndrome: Premature aging due to

replication-associated telomere loss

- Solution: Telomeres!
o Telomere: Serves as molecular buffer. Telomeres are added at the 3’
end of parental DNA so that end replication problem would eat into
telomeres instead of expressed genes. Allows the cell to divide many
more times, before expressed genes are eroded.
o Made of G-rich non coding sequence
o Telomerase: Synthesizes telomeres so DNA can replicate infinitely.
DNA Repair mechanisms

Process How When

Proofreading DNA Polymerase III Proofreads DNA as it Immediate
replicates and immediately replaces wrong
bases
Mismatch repair Mismatched bases removed by mismatch repair After DNA replication
proteins, DNA polymerase I adds right bases
Excision repair Damaged DNA (eg smoking) removed by Over lifetime of cell
excision repair proteins, DNA polymerase I
replaces bases
RNA

RNA DNA

Ribose Sugar Deoxyribose Sugar

Uracil Thymine
Single stranded Double stranded

Transcription

First level of control: Acetylation of histones

- Histone acetyltransferases add acetyl groups to histone which neutralises its

positive charge
- Binds less tightly to negatively charged DNA phosphate backbone, loosens
DNA (decondenses)
- Increased accessibility of RNA polymerase  Increased transcription of
genes
- Conversely, histone deacetylases removes acetyl making DNA condense thus
reducing transcription

DNA Methylation

- Methyl group covalently added to cytosines  reduced transcription of genes

the methyl groups are added to

Initiation

- Promoters signal to RNA polymerase where to bind (which is the template

strand and location)

Elongation

- RNA polymerase unwinds DNA and

synthesizes complementary RNA
from 5’ to 3’.
- As transcript forms, it peels away
from DNA, allowing transcribed DNA
to rewind into double helix
- Energy comes from removal and
breakdown of pyrophosphate group
from each ribnucleoside
triphosphate (red molecule)
Termination

- Terminator DNA sequence signals for termination of transcription. Once it is

transcribed, transcription ends.
- Sequence signalling for polydenylation (poly-a tail) is transcribed before
terminator DNA sequence is reached

Types of RNA (All synthesized by transcription)

- mRNA: Translated to proteins in ribosome

- rRNA: Contributes to ribosome structure and function
- tRNA: Adds specific amino acids to the growing polypeptide chain in
translation

Processing stage (Removal of introns)

- Removed by spliceosomes

Altered by adding poly a tail and cap

Protein

tRNA

 At 3’ end of tRNA, amino acids

covalently bond to yellow section 


 tRNA has anti-codons on “arm” that

will attach to the right codon of
mRNA

4 steps
- Charging
- Initiation
- Elongation
- Termination

mRNA enters ribosome from the 5’ end, amino acids are added from 5’ to 3’.
Proteins

Codons

 Start (AUG): Methionine

 Stop: UAA, UAG, UGA