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Full-Text Articles in Life Sciences
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 Modulated By Dna Repair Enzymes And Cofactors, Yaou Ren
Trinucleotide Repeat Instability Modulated By Dna Repair Enzymes And Cofactors, Yaou Ren
FIU Electronic Theses and Dissertations
Trinucleotide repeat (TNR) instability including repeat expansions and repeat deletions is the cause of more than 40 inherited incurable neurodegenerative diseases and cancer. TNR instability is associated with DNA damage and base excision repair (BER). In this dissertation research, we explored the mechanisms of BER-mediated TNR instability via biochemical analysis of the BER protein activities, DNA structures, protein-protein interaction, and protein-DNA interaction by reconstructing BER in vitro using synthesized oligonucleotide TNR substrates and purified human proteins. First, we evaluated a germline DNA polymerase β (pol β) polymorphic variant, pol βR137Q, in leading TNR instability-mediated cancers or neurodegenerative diseases. We find …
Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Arts & Sciences Electronic Theses and Dissertations
Faithful DNA replication and repair are essential for maintaining genome stability and preventing various diseases including cancer. Both processes are executed by numerous redundant mechanisms to ensure that these processes are uninterrupted even when a primary mechanism fails. Despite this, they are not immune to challenges and failures leading to DNA damage and genome instability. These problems are more evident at the difficult-to-replicate regions of the genome such as the telomeres that cap and protect linear chromosome ends. Additionally, topological structures such as RNA:DNA hybrids, commonly referred to as R loops, can also present severe challenges to the DNA replication …