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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Dna Base Excision Repair Modulates Dna Repeat Instability And Non-B Form Dna Structures, Eduardo E. Laverde
Dna Base Excision Repair Modulates Dna Repeat Instability And Non-B Form Dna Structures, Eduardo E. Laverde
FIU Electronic Theses and Dissertations
The human genome is constantly attacked by endogenous and exogenous sources of DNA damage that generates DNA base lesions and strand breaks leading to genome instability, cell death, and diseases. To combat these adverse effects, cells have evolved a robust DNA repair mechanism called “the DNA base excision repair (BER),” which efficiently removes DNA lesions maintaining genome stability. However, its underlying molecular mechanisms remain to be elucidated. In my dissertation research, I explored the molecular mechanism by which BER modulates trinucleotide repeats (TNR) by processing non-B form structures such as hairpins and R-loops through the coordination among BER enzymes and …
Trinucleotide Repeat Instability Is Modulated By Dna Base Lesions And Dna Base Excision Repair, Jill M. Beaver
Trinucleotide Repeat Instability Is Modulated By Dna Base Lesions And Dna Base Excision Repair, Jill M. Beaver
FIU Electronic Theses and Dissertations
Trinucleotide repeat (TNR) expansions are the cause of over 40 human neurodegenerative diseases, and are linked to DNA damage and base excision repair (BER). We explored the role of DNA damage and BER in modulating TNR instability through analysis of DNA structures, BER protein activities, and reconstitution of repair using human BER proteins and synthesized DNA containing various types of damage. We show that DNA damage and BER can modulate TNR expansions by promoting removal of a TNR hairpin through coordinated activities of BER proteins and cofactors. We found that during repair in a TNR hairpin, coordination between the 5’-flap …