Abasic sites (Ap site, from apurinic/apyrimidinic) are one of the most common lesions generated in DNA by spontaneous base loss or DNA repair processes. There are two equilibrating forms of an Ap site - ring-open aldehyde and cyclic hemiacetal. Ring- opened aldehydes are reactive electrophilic groups capable of formation covalent adduct with nucleophilic sites in DNA. DNA interstrand cross-link (ICL) resulting from the Ap sites is formed spontaneously as a covalent bond between ring-open aldehyde and amin group of adenin residue in the opposite strand of double stranded DNA. ICLs block DNA replication and transcription. The formation of Ap site derived ICL is relatively long process taking several hours. We assume that the ring-opening of an abasic site is the rate-limiting step in the formation of the thermodynamic ICL. However, formation, stability and DNA repair of Ap-ICL are still poorly understood processes. Here, I have set up mechanistic in vitro experiments to reveal and calculate the probability of Ap-ICl formation in vivo. In more detail, I study the rates of formation of Ap-ICLs in the sequence context of neighbouring nucleotides of freshly formed covalent bond of ICL. I focus on sequence preference, the influence of AT/ GC rich regions and the length of oligonucleotides. I have...
| Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:397027 |
| Date | January 2019 |
| Creators | Landová, Barbora |
| Contributors | Šilhán, Jan, Lux, Vanda |
| Source Sets | Czech ETDs |
| Language | Czech |
| Detected Language | English |
| Type | info:eu-repo/semantics/masterThesis |
| Rights | info:eu-repo/semantics/restrictedAccess |
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