THESIS
2017
xii, 67 pages : illustrations ; 30 cm
Abstract
Apurinic/apyrimidinic sites, also called the abasic sites, are the most commonly found lesions
in DNA and they are reported to be mutagenic and carcinogenic. Abasic sites can be induced by
spontaneous hydrolysis, physical treatments as well as chemical treatments by cleavage of N-glycosidic
bonds. After that, there will be loss of nucleobases, forming a ribosyl moiety which is
in equilibrium between a ring-closed and a ring-opened structure.
Abasic sites are mutagenic and carcinogenic because of the highly reactive carbonyl group in
the ring-opened structure. However, if the abasic sites are not being repaired, they are even in
greater mutagenic potential and can lead to severe biological consequences. The highly reactive
ring-opened form of abasic site can react with biomac...[
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Apurinic/apyrimidinic sites, also called the abasic sites, are the most commonly found lesions
in DNA and they are reported to be mutagenic and carcinogenic. Abasic sites can be induced by
spontaneous hydrolysis, physical treatments as well as chemical treatments by cleavage of N-glycosidic
bonds. After that, there will be loss of nucleobases, forming a ribosyl moiety which is
in equilibrium between a ring-closed and a ring-opened structure.
Abasic sites are mutagenic and carcinogenic because of the highly reactive carbonyl group in
the ring-opened structure. However, if the abasic sites are not being repaired, they are even in
greater mutagenic potential and can lead to severe biological consequences. The highly reactive
ring-opened form of abasic site can react with biomacromolecules in close proximity to form
crosslinks like DNA-DNA intra cross-links and DNA-protein cross-links. Covalently bonded biomacromolecules can interrupt several metabolic processes like DNA replication, recombination
and transcription. Without appropriate repair of the cross-links can finally lead to cell apoptosis.
The study of the formation of abasic site in both DNA and RNA and its DNA-protein
crosslinks are of great importance in understanding related human diseases. The goal of my first
project is to apply the developed LC-MS/MS method of high sensitivity and selectivity to
quantitate the amount of abasic site from spontaneous hydrolysis as well as to study the formation
rate of abasic site in both DNA and RNA under the exposure of chemicals. It is anticipated that
the method can be used for assessing the risk of related human diseases. The goal of my second
project is to find out a suitable biomarker for the detection of DNA-protein cross-links (DPCs) in
biological systems by using LC-MS/MS system. It is anticipated that the biomarker found can be
used for the quantitation of DNA-protein cross-links as well as for the study of related human
diseases.
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