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Oxidative Dna Damage Modulates Trinucleotide Repeat Instability Via Dna Base Excision Repair, Meng Xu
Oxidative Dna Damage Modulates Trinucleotide Repeat Instability Via Dna Base Excision Repair, Meng Xu
FIU Electronic Theses and Dissertations
Trinucleotide repeat (TNR) expansion is the cause of more than 40 types of human neurodegenerative diseases such as Huntington’s disease. Recent studies have linked TNR expansion with oxidative DNA damage and base excision repair (BER). In this research, we provided the first evidence that oxidative DNA damage can induce CAG repeat deletion/contraction via BER. We found that BER of an oxidized DNA base lesion, 8-oxoguanine in a CAG repeat tract, resulted in the formation of a CTG hairpin at the template strand. DNA polymerase β (pol b) then skipped over the hairpin creating a 5’-flap that was cleaved by flap …