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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 …
Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang
Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang
FIU Electronic Theses and Dissertations
DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, …
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 …
Roles Of Dna Base Excision Repair In Maintaining The Integrity Of Dna Methylation, Jing Zhou
Roles Of Dna Base Excision Repair In Maintaining The Integrity Of Dna Methylation, Jing Zhou
FIU Electronic Theses and Dissertations
DNA methylation and demethylation are involved in regulation of gene expression. CpG clusters have been identified as hotspots of oxidative damages and mutagenesis. DNA base excision repair can remove oxidative DNA damage on CpG clusters and mediate an active DNA demethylation pathway. In this study, we examined the molecular mechanisms underlying interactions among DNA methylation, demethylation and BER. Our results demonstrated that a single 5-methylcytosine did not exhibit a significant effect on BER. Surprisingly we found that the abasic site completely inhibited the activity of thymine DNA glycosylase (TDG) leading to the sustainment of the mismatch efficiently extended by pol …