Physical Sciences and Mathematics Commons^™

A 5', 8-Cyclo-2'-Deoxypurine Lesion Induces Trinucleotide Repeat Deletion Via A Unique Lesion Bypass By Dna Polymerase Β., Meng Xu, Yanhao Lai, Zhongliang Jiang, Michael A. Terzidis, Annalisa Masi, Chryssostomos Chatgilialoglu, Yuan Liu

Department of Chemistry and Biochemistry

5′,8-cyclo-2′-deoxypurines (cdPus) are common forms of oxidized DNA lesions resulting from endogenous and environmental oxidative stress such as ionizing radiation. The lesions can only be repaired by nucleotide excision repair with a low efficiency. This results in their accumulation in the genome that leads to stalling of the replication DNA polymerases and poor lesion bypass by translesion DNA polymerases. Trinucleotide repeats (TNRs) consist of tandem repeats of Gs and As and therefore are hotspots of cdPus. In this study, we provided the first evidence that both (5′R)- and (5′S)-5′,8-cyclo-2′-deoxyadenosine (cdA) in a CAG repeat tract caused CTG repeat deletion exclusively …

Base Excision Repair Of Chemotherapeutically-Induced Alkylated Dna Damage Predominantly Causes Contractions Of Expanded Gaa Repeats Associated With Friedreich's Ataxia, Yanhao Lai, Jill M. Beaver, Karla Lorente, Jonathan Melo, Shyama Ramjagsingh, Irina U. Agoulnik, Zunzhen Zhang, Yuan Liu

Department of Chemistry and Biochemistry

Expansion of GAA·TTC repeats within the first intron of the frataxin gene is the cause of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disorder. However, no effective treatment for the disease has been developed as yet. In this study, we explored a possibility of shortening expanded GAA repeats associated with FRDA through chemotherapeutically-induced DNA base lesions and subsequent base excision repair (BER). We provide the first evidence that alkylated DNA damage induced by temozolomide, a chemotherapeutic DNA damaging agent can induce massive GAA repeat contractions/deletions, but only limited expansions in FRDA patient lymphoblasts. We showed that temozolomide-induced GAA repeat instability …

Conformational Dynamics Associated With Ligand Binding To Vertebrate Hexa-Coordinate Hemoglobins, Luisana Astudillo

FIU Electronic Theses and Dissertations

Neuroglobin (Ngb) and cytoglobin (Cygb) are two new additions to the globin family, exhibiting heme iron hexa-coordination, a disulfide bond and large internal cavities. These proteins are implicated in cytoprotection under hypoxic-ischemic conditions, but the molecular basis of their cytoprotective function is unclear.

Herein, a photothermal and spectroscopic study of the interactions of diatomic ligands with Ngb, Cygb, myoglobin and hemoglobin is presented. The impact of the disulfide bond in Ngb and Cygb and role of conserved residues in Ngb His64, Val68, Cys55, Cys120 and Tyr44 on conformational dynamics associated with ligand binding/dissociation were investigated. Transient absorption and photoacoustic calorimetry …