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Mutation types
ACERCA DE MUTAES
Sistemas de reparao
Mutation might also occur during DNA replication
Wilde-type
Mutant
Two basic classes of mutations: somatic and
germ-line mutation
Reproductive cells
Three basic molecular types of gene mutations are
base substitutions, insertions and deletions
Base substitution leads to two types of molecular change:
transition and tranversion
Ponctual mutations
Molecular basis of sickle-cell anemia. Consequences of
base substitution example- missense mutation
The resulting hemoglobin is defective and tends to polymerize at low oxygen concentration
Insertion/deletion of a nucleotide
Frameshift mutation
Other classifications for phenotypic effects of
mutations
Tautomerization
Depurination
keto enol
C=O C-OH
keto enol
amino imino
-NH2 =NH
amino imino
Pairing relationships of DNA bases in the normal and tautomeric
forms
(imino)
(enol)
Tautomeric shifts results in transition mutations. The tautomerization can occur in the:
- template base, ie, tautomerization of the base in the template
- substrate base, ie, tautomerization of incoming base.
Depurination
Desaminao
Espontnea ou induzida
Deamination: spontaneous loss of
amino group
Methylated cytosine
Methylation of cytosine at the number-5 position in the
base. The methyl donor is S-adenosylmethyonine
Mechanism by which uracil-containing nucleotides
are formed in DNA and removed (E. coli)
The deoxyribose with the uracil detached is then excised from the DNA backbone
by another enzyme (AP endonuclease) and the gap is repaired
Ex.
Base analogs (ex. 5-Bu, 2-AP)
Chemicals that alter bases
Nitrous acid- deamination
Alkylating agents (EMS, NTG, nitrogen mustards, mitomycin C)
Hydroxylamine
Intercalating agents (EtBr, proflavin )
Reactive forms of oxygen (ex superoxide radicals)- oxidative
reactions
Base analogues
(ex)
Transition
A-T G-C
Pu-Py Pu-Py
INTERCALATING AGENTS
UV
Ionizing radiation
Heat
In the electromagnetic spectrum, as wavelenght decreases, energy increases
Ionizing radiation
sunlight
/TV
Pyrimidime dimers result from ultraviolet light
Mechanism of mutagenesis:
single and double-stranded breaks in DNA
damage to nucleotides
Tcnicas de Mutagnese
Aleatria (random)
Dirigida
deamination
Chemical mutagenesis
using sodium bisulfite
- ADA in E.coli
- MGMT (O6-methylguanine-DNA methyltransferase)
in humans
Base and nucleotide excision repair
Excises modified bases and then
replaces the entire nucleotide
Nick
Just after DNA replication Many incorrectly inserted nucleotides that
escape proofreading are corrected by
MutHLS - mismatch repair
Dam methylase
Excision repair of DNA by
E. coli UvrABC mechanism