Life Sciences Commons^™

Functional Analysis Of Stn1 Winged-Helix (Wh) Domains, Anna Bazell

Senior Theses

CST (CTC1-STN1-TEN1) is a heterotrimeric RPA-like protein complex that preferentially binds to single-stranded DNA (ssDNA). CST is conserved from yeast to humans and has been found to play a role in telomere maintenance, DNA replication, and DNA repair. Mutations in CST, specifically in the subunits of CTC1 and STN1, have been implicated in the development of the genetic diseases Coats plus and dyskeratosis congenita. Despite the known functions of CST, the mechanistic relationship between its structure and function has yet to be characterized, particularly with respect to its protein-protein interactions and DNA binding. An X-ray crystallography structure of CST revealed …

Dna Lesions Produced From The Reaction Of Diols And 5-Formylcytosine And Their Effects On Dna Replication, Brock Allen

University of the Pacific Theses and Dissertations

Nucleic acids are complex macromolecules that are susceptible to both endogenous and exogenous damage. This study explored damage resulting from interactions with environmental nucleophilic toxins, such as a variety of diols and amines found in industry. These nucleophiles can react with electrophilic groups, such as 5-formylcytosine. 5-formylcytosine is an oxidation product of the epigenetic base 5-methylcytosine. It is typically removed by thymine DNA glycosylase (TDG) but is known to accumulate in the genome, making the formyl group susceptible to attack. In this study we used GC/MS and ESI-MS to show that DNA lesions from the nucleophilic addition reaction of toxins …

Analysis Of Chromatin Accessiblity Of The Human C-Myc Replication Origin, Tu Thien Danh

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The best characterized eukaryote replication model is of the budding yeast Saccharomyces cerevisiae. Replication origins of S.cerevisiae are 100 to 200 bp in size and contain an essential 11-bp autonomous replicating sequence (ARS) consensus sequence (ACS). The origin recognition complex (ORC) binds to the ACS in order to recruit additional replication factors (Cdt1, Cdc6, MCM, Cdc45) and together they form the pre-replication complex (pre-RC).

Unlike budding yeast, the mammalian cells contain dispersed replication origins in which multiple elements distributed over large distances act as replication start sites. Mammalian DNA replication origins, such as the c-myc origin, contain a DNA unwinding …

Due-B, A New Human Dna Replication Protein, Is The Functional Homolog Of S. Cerevisiae Sld3, Jianhong Yao

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DNA unwinding elements (DUEs) are commonly found at DNA replication origins. The DUE binding protein (DUE-B) is crucial for the initiation of DNA replication in eukaryotes. The unique 59 amino acid C-terminal part of DUE-B shares nearly 50% similarity with yeast the C-terminus of Sld3. DUE-B plays a key role in eukaryotic DNA replication because it is required for the loading of Cdc45, the MCM helicase activator, on chromatin. Here we show that DUE-B, just like yeast Sld3, binds to Cdc45 and TopBP1 through its C-terminus in Sf9 cells and in vitro. We also show that DUE-B, Cdc45 and TopBP1 …