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Mutagenesis
Mutation: replication fidelity, mutagens,
mutagenesis
DNA damage
DNA lesions: oxidative damage, alkylation, bulky
adducts
DNA repair
Photoreaction, alkyltransferase, excision repair,
mismatch repair, hereditary repair defects
DNA damage, repair & Mutagenesis
1 Mutagenesis
Mutation
Replication fidelity
Mutagens: chemical & physical
Mutagenesis: direct & indirect
Mutation
Replication Mutagenesis
Fidelity
Mutagens
1 Mutaagenesis
1-1 Mutation
Permanent, heritable alterations
in the base sequence of DNA
Reasons
1. Spontaneous errors in DNA replication or meiotic
recombination
2. A consequence of the damaging effects of physical
or chemical mutagens on DNA
1 Mutaagenesis
Point mutation
(a single base change)
Transition : Purine or pyrimidine is replaced
by the other AG T C
Phenotypic
effects
Noncoding DNA
Nonregulatory DNA Silent mutation No
3rd position of a codon
Insertions or deletions
The addition or loss of one or more bases in a DNA region
Frameshift mutations
The translation of a protein encoded gene is
frameshifted , then changed the C-terminal side of the
mutation is completely changed.
Examples of deletion mutations
1 Mutaagenesis
Mutation relevant
1. Spontaneous errors in DNA replication is very rare, one
error per 1010 base in E. coli.
1 Mutaagenesis
Proofreading
by
E. coli polymerase
1 Mutaagenesis
Mutagens
Mutation relevant
Cause DNA damage that can be converted to mutations.
1 Mutaagenesis
Physical mutagens
High-energy ionizing radiation: X-rays and g-rays
strand breaks and base/sugar destruction
Nonionizing radiation : UV light pyrimidine dimers
Chemical mutagens
Base analogs: direct mutagenesis
Nitrous acid: deaminates C to produce U
Alkylating agents
Lesions-indirect mutagenesis
Intercalating agents
Base analogs: derivatives of the normal bases
incorporated in DNA, altering base pairing properties.
Mutagenesis
The molecular process
in which the mutation is generated.
Direct mutagenesis
Indirect mutagenesis
The mutation is introduced as a result
of an error-prone repair.
Translesion DNA synthesis to
maintain the DNA integrity but not
the sequence accuracy: when damage
occurs immediately ahead of an advancing
fork, which is unsuitable for recombination
repair
the daughter strand is synthesized
regardless of the the base identity of the
damaged sites of the parental DNA.
1 Mutaagenesis
E. coli translession replication: SOS
response: Higher levels of DNA damage
effectively inhibit DNA replication and trigger a
stress response in the cell, involving a regulated
increase (induction) in the levels of a number of
proteins. This is called the SOS response.