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Types of damage
There are five main types of damage to DNA due to endogenous cellular
processes:
oxidation of bases [e.g. 8-oxo-7,8-dihydroguanine (8-oxoG)] and generation of
DNA strand interruptions from reactive oxygen species,
alkylation of bases (usually methylation), such as formation of 7-
methylguanine, 1-methyladenine, 6-O-Methylguanine
hydrolysis of bases, such as deamination, depurination, and depyrimidination.
DNA UNDERGOES DAMAGE
SPONTANEOUSLY FROM
HYDROLYSIS(Ë®½â) AND
DEAMINATION(È¥°±»ù)
? This is ironic since the proper structure of the double helix depends on
an aqueous environment.
Deamination
C-U
Depurination
---->
an abasic site
Deamination of
5-mC---->T
DNA IS DAMAGED BY
ALKYLATION, OXIDATION, AND
RADIATION
Often mispqir with thymine
G:C ¨CA:T
Reactive oxygen species
O2-, H2O2, OH?
G modification (alkylation & oxidation)
Thymine dimer by ultraviolet light
Incapable of base-pairing and cause the DNA
polymerse to stop during replication
Clastogenic ¨C ionizing radiation and agents like
bleomycin that cause DNA to break are said to be
clastogenic.
MUTATIONS ARE ALSO
CAUSED BY BASE ANALOGS
AND INTERCALATING AGENTS
Base analogues
Intercalating agents which cause the deletion or
addition of a base pair or a few base pairs
DNA DAMAGE
DNA undergoes damage
spontaneously from hydrolysis
and deamination
DNA is damaged by alkylation, oxidation, and radiation
Thymine dimer caused by UV light
Base analogs and intercalating agents that cause
mutations in DNA
Ames test for carcinogens
Bruce N. Ames
Professor of the Graduate School Division of Biochemistry and Molecular Biology,
UC Berkeley
REPAIR OF DNA DAMAGE

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