MOLECULAR BASIS OF GENETICS

DNA is a
combination of 4
possible bases,
bound in pairs in
a double helix
 Genetics…Just the Basics
Definitions
 study of the underlying basis of heredity and variation.
 the study of how
 traits are inherited from one generation to another
 genes are organized and expressed
 genes behave in populations and evolve over time.
 Genetics plays a central role in all modern biology and
is essential for an understanding of the living world.
 Management of Genetic Information
Three major stages
The Central Dogma
1. DNA replication – identical molecules
2. Transcription – DNA copied into mRNA
3. Translation – codons in the mRNA direct the amino acid sequence in the
protein
 Nucleic acid Structure
5-Carbon sugar

2’deoxyribose ribose
Nitrogenous base

purine pyrimidine

Phosphate group
SUGARS
NITROGENOUS BASES
Nucleoside
Sugar + base
Nucleotide…adding a spoonful of sugar and a pinch of
phosphate on a base
 Sugar + base + phosphate
Nomenclature of Nucleosides

Base Nucleoside (DNA Nucleoside (RNA) Abbreviation

Adenine Deoxyadenosine Adenosine A

Guanine Deoxyguanosine Guanosine G

Cytosine Deoxycytidine Cytosine C

Thymine Deoxythymidine --- T

Uracil --- Uridine U

 Nucleotide nomenclature

DNA RNA
Base monoPO4 diPO4 triPO4 monoPO4 diPO4 triPO4

Adenine deoxyAMP deoxyADP deoxyATP AMP ADP ATP

Guanine deoxyGMP deoxyGDP deoxyGTP GMP GDP GTP

Cytosine deoxyCMP deoxyCDP deoxyCTP CMP CDP CTP

Thymine deoxyTMP deoxyTDP deoxyTTP

Uracil UMP UDP UTP

Complementary Base pairing (Chargaff’s Rule)
Complementary Base pairing
Complementary Base pairing

O
Complementary Base pairing
 How many (%) T if there is 33% of G?
 How many (%) G if there is 20% of A?
Antiparallel orientation
 DNA Replication
 DNA Helicases-facilitate separation of double stranded

DNA

 DNA single-stranded binding proteins (SSBP)-

protect separated DNA strands from the free radicals

and enzymes that attack the nucleic acids
 DNA Gyrase/ DNA topoisomerase- will remove the tension
created along the unwinding DNA
 Primase- synthesis the primer

 DNA Polymerase –
 DNA polymerase III.-add up nucleotides to the growing DNA strand
 DNA Polymerase I (Pol I)-remove the primer

 DNA Ligase-joins/anneals the okazaki fragments (lagging

strands)
Start of DNA replication
LEADING STRAND-
synthesized
continuously, no
interruption

LAGGING
STRAND/OKAZAKI
FRAAGMENTS-
synthesized
semicontinuously
 DNA polymerases
 Five DNA polymerases have been found to exist in E.
coli
 Pol I is involved in synthesis and repair, removal of primers
 Pol II, IV, and V are for repair under unique conditions
 Pol III is primarily responsible for synthesis of new DNA
strands
 Semiconservative
replication describe
s the method by
which DNA is
replicated in all
known cells.

 produce two copies

that each contained
one of the original
strands and one new
strand
 Semi-conservative replication
 Strand separation
 Double stranded DNA: old and new strands

3’ 5’
A T C C G T G A G G T C T A G C T
5’ T A G G C A C T C C A G A T C G A 3’
 Template strand
3’ A T C C G T G A G G T C T A G C T 5’
5’ T A G G C A C T C C A G A T C G A 3’
New strand
RNA: DNA’s Close Cousin
DNA TRANSCRIPTION/RNA SYNTHESIS
RNA has three major characteristics that make it different from DNA

 RNA is very unstable

and decomposes
rapidly
 RNA contains URACIL
in place of THYMINE
 RNA is almost always
single-stranded
 Types of RNA

 Messenger RNA (mRNA)

 Ribosomal RNA (rRNA)
 Transfer RNA (tRNA)
 TRANSCRIPTION

Template strand(antisense strand)

3’ 5’
A T C C G T G A G G T C T A G C T
T
U A G G C A C T
U CC CC A
A G
G A
A T
U CC GG AA mRNA
5’ 3’

Sense strand( has the gene sequence)

 Promoter region

RNA pol and sigma

subunit/sigma factor
 TRANSLATION

CGU AUG AGG CAC UCC AGA UCG UAG

met ---arg---his ---ser --arg----ser--(stop)
polypeptide
 GENETIC CODE
 Triplet codes=codon
 Nonoverlapping
 Commaless
 Degenerate
 Almost universal
 Start codon and
stop codons
INITIATION ELONGATION TERMINATION
 Post-Translational Modification
 New polypeptide is nonfunctional
 Folding
 Removal or cleavage of some amino acid residues
 Glycosylation, phosphorylation, acetylation, etc
Flow of genetic information
 MUTATION

MUTATION - a change in the base

sequence of DNA

-may be spontaneous or induced

 MUTAGENS

 Physical Agents
 UVL – pyrimidine dimers*
 Ionizing radiation – (x-rays, gamma rays)- forms highly
reactive free radicals leading to single-stranded breaks
*
 Chemical Agents
 Nitrous acid
 Intercalating agents
 5-bromouracil *
 UVL

#
 Ionizing Radiation

#
Chemical agents

#
 MUTATION
 Substitution
 Transition – Purine → Purine (A → G);
Pyrimidine → Pyrimidine (T → C)

 Transversion – Purine → Pyrimidine (G →T);

vice versa (C → A)
Single Base substitution is called POINT MUTATION
 Mutation-POINT MUTATION
 Missense mutation
 Base substitution in DNA results to replacement
of 1 amino acid residue by another in a protein

AGU-CGU-GGA-AAU-UGU-CCU-CGA-
ser - arg - gly - asn - cys - pro - arg
AGU-CGU-GCA-AAU-UGU-CCU-CGA-
ser - arg - ala - asn - cys - pro - arg
 Mutation-POINT MUTATION
 Nonsense mutation
 If base substitution creates a stop codon, thereby
terminates protein synthesis prematurely

AGU-CGU-GGA-AAU-UGU-CCU-CGA-
ser - arg - gly - asn - cys - pro - arg
AGU-CGU-UGA-AAU-UGU-CCU-CGA-
ser - arg -stop
 Mutation-POINT MUTATION
• Silent mutation
- substitution results in triplet coding for the same
amino acid as the original triplet (redundancy of the
genetic code)
- change usually occurs at the 3rd base
AGU-CGU-GGA-AAU-UGU-CCU-CGA-
Wobble effect
ser - arg - gly - asn - cys - pro - arg
AGU-CGU-GGU-AAU-UGU-CCU-CGA-
ser - arg - gly - asn - cys - pro - arg
 GENETIC CODE
 Degeneracy of
Genetic code
 Mutation-INDELS
 Frameshift mutation
 Due to insertion mutation or deletion mutation
A

AGU-CGU-GGA-AAU-UGU-CCU-CGA-
ser - arg - gly - asn - cys - pro - arg -
AGU-CGU-GAG-AAA-UUG-UCC-UCG-A-
ser - arg - glu - lys - leu - ser - ser
 REPAIR MECHANISMS

 Photoreactivation (Light repair)

 Excision repair
 Post replication repair
LIGHT REPAIR
EXCISION REPAIR OR DARK REPAIR
Exercise